





































Berkeley
Pharma Tech
Journal of Medicine

Correspondence: 
nethra.srinivasan22@gmail.com 

Keywords:
Precision Medicine, Alzheimer’s, 
Schizophrenia, iPSC, 
Pharmacogenomics, Genetic 
Profiling, Neurological Disease

Submitted February 9, 2024 
Accepted March 29, 2024
Published June 28, 2024

Full Open Access

Creative Commons Attribution 
License 4.0

Abstract
There exist over 600 neurological conditions, each characterized by unique pathologies 
tailored to individual patients. Over the past two decades, advances in biotechnology 
have propelled the field of neurogenetics forward. This progress has illuminated 
therapeutic targets and methodologies tailored to the specific needs of each patient. 
Current treatment options primarily encompass therapies and conventional 
medications like cholinesterase inhibitors for Alzheimer’s disease and antipsychotics 
for schizophrenia. However, these treatments often address symptoms or general 
targets rather than the precise underlying causes. Precision medicine has emerged as a 
promising approach in both animal and human clinical trials. Examples include the 
identification of specific genetic variations linked to Alzheimer's risk and progression, 
as well as the application of multigenic pharmacogenomics-guided therapies for 
schizophrenia patients. This review paper delves into the role of precision medicine in 
neurogenetics, focusing on neural stem cells, induced pluripotent stem cells (iPSCs), 
genetic profiling, and pharmacogenetics within the contexts of Alzheimer’s disease and 
schizophrenia. By evaluating current achievements alongside existing challenges, this 
paper underscores precision medicine as a pivotal strategy for effectively targeting 
neurological disorders.

Neurogenetics: Precision Medicine-Based 
Approaches to Neurological Disorders 
with an Emphasis on Addressing 
Alzheimer’s Disease and Schizophrenia
By: Nethra Srinivasan, Eshaan Mehra, Sriya Dommaraju, Ethan Kakavetsis



1. Introduction

As we delve into the secrets of the human mind, one thing becomes 
abundantly clear: our genes hold the key to understanding the most 
profound mysteries of consciousness. Neurogenetics is employing the 
evolving �eld of genomics–the study of our genes and genetic variations–to 
understand factors contributing to the structure and function of the 
nervous system.1 Speci�cally, neurogenetics also seeks to understand how 
alterations in genes can lead to neurological diseases and conditions. As 
researchers continue to uncover various genetic factors for each disorder, 
precision medicine has started to address neurological diseases.

Precision medicine is an approach to therapeutics that uses an individual’s 
genomic, environmental, and lifestyle information to form decisions about 
their treatment.2 Often informally termed as personalized medicine, 
precision medicine can be used to create a more precise approach to 
diagnose, prevent, or treat a disease. The basis behind precision medicine is 
substantial because the human genome consists of about 3 billion base pairs 
of DNA, and no two humans are genetically identical, with genetic 
variation of about 0.1 percent.3 This means that about 6 million base pairs 
di�er, making it necessary to understand genetic variation. Oftentimes, 
these variations occur as single-nucleotide polymorphisms, or single-base 
pair di�erences.3 To target these various genetic risk factors, techniques of 
precision medicine such as drugs tailored to genomic or metabolomic 
targets and induced pluripotent stem cells (iPS) are promising 
methodologies.

While understanding the hallmark genes of neurological disorders through 
neurogenetics studies may help create therapeutics for these genes, many 
studies tend to exclude non-White individuals. Research involving diverse 
populations reveals varying prevalence rates of risk genes for Opioid Use 
Disorder (OUD) based on ethnicity, with speci�c genetic variations being 
linked to susceptibility in Caucasian individuals but not in 
African-American or Hispanic populations.4 This evidence suggests that 
there are larger implications in other neurogenetic diseases such as 
Alzheimer’s disease and Schizophrenia. There exist multiple polymorphisms 
in a diverse society, making neurogenetics a complicated �eld. We ought to

Berkeley Pharma Tech Journal of Medicine | 15

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630880/
https://www.genome.gov/genetics-glossary/Precision-Medicine
https://www.ncbi.nlm.nih.gov/books/NBK20363/
https://www.ncbi.nlm.nih.gov/books/NBK20363/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457418/#:~:text=Studies%20that%20include%20diverse%20populations,or%20SUDs%2C%20and%20vice%20versa.


adopt precision medicine-based management through analyzing 
ancestry-based genetic information to provide the best precision-guided 
therapeutics. Variance in neurogenetics presumes the need for precision 
medicine to target genetic risk factors with tailored medicine speci�c to the 
patient with neurological diseases, such as Alzheimer’s disease and 
schizophrenia. We present our evaluations by analyzing scienti�c literature 
on varied neurological disorders and diseases and their basis in 
neurogenetics, reviewing the scienti�c literature for recent advances in 
precision medicine, and examining clinical trials to understand the potency 
of precision medicine techniques in neurological conditions.

2. Variance in Neurogenetics

2.1 Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive and irreversible neurological 
disorder that a�ects the brain, leading to a decline in memory, thinking, and 
ability to carry out simple tasks.5 This decline in cognitive ability hasn’t been 
attributed to a speci�c cause due to the complexity of the genetic and 
environmental causes of this disease.

2.1.1 Amyloid Beta (Aβ): Formation of Amyloid Plaques

β- amyloid proteins are known to be one of the main culprits of 
Alzheimer’s Disease. They collect between neurons and inhibit neuronal 
function, and some molecular forms of these defunct proteins form plaques 
that are extremely detrimental to neuronal activity.6

2.1.2 Tau Protein: Formation of Neuro�brillary Tangles

Neuro�brillary tangles are clusters of abnormal proteins called tau which 
accumulate within nerve cells.6 In healthy neurons, microtubules provide 
internal support for the function of transporting nutrients and molecules 
from the cell body to the axon and dendrites.6 Tau usually binds to and 
stabilizes these microtubules; however, in AD, chemical changes cause tau 
to detach from microtubules and adhere to other tau molecules, forming 
threads.6 These amalgamate to form tangles within neurons, disrupting the 
neuron’s transport system and impairing synaptic communication.6

Berkeley Pharma Tech Journal of Medicine | 16

https://www.nia.nih.gov/health/what-alzheimers-disease
https://pubmed.ncbi.nlm.nih.gov/24493463/#:~:text=The%20soluble%20building%20blocks%20of,%2Denriched%20microtubule%2Dassociated%20protein.
https://pubmed.ncbi.nlm.nih.gov/24493463/#:~:text=The%20soluble%20building%20blocks%20of,%2Denriched%20microtubule%2Dassociated%20protein.
https://pubmed.ncbi.nlm.nih.gov/24493463/#:~:text=The%20soluble%20building%20blocks%20of,%2Denriched%20microtubule%2Dassociated%20protein.
https://pubmed.ncbi.nlm.nih.gov/24493463/#:~:text=The%20soluble%20building%20blocks%20of,%2Denriched%20microtubule%2Dassociated%20protein.
https://pubmed.ncbi.nlm.nih.gov/24493463/#:~:text=The%20soluble%20building%20blocks%20of,%2Denriched%20microtubule%2Dassociated%20protein.


Evidence has shown that these plaques and tangles are associated with the 
occurrence of Alzheimer’s disease, as represented in Figure 1, and that the 
occurrence of either plaques or tangles can cause the formation of the 
other.6

Figure 1. A visual representation of Alzheimer’s disease manifests in patients because of 
genes that are prime targets for precision medicine techniques. The result of mutations or 
rare variants in certain genes, such as ApoE4, can have many harmful e�ects that manifest as 
Alzheimer’s disease.9

2.1.3 Glial Cell interaction with Aβ

Microglia act as immune cells that monitor the brain for signs of damage, 
infection, or foreign substances.7 When threats are detected, they activate 
and engulf via phagocytosis, cellular debris, aggregated proteins, etc.7 

Microglia have the ability to detect the presence of Aβ in the brain.8 When 
encountered with Aβ plaques in healthy cells, they become reactive, 
indicating they are responding to abnormal protein accumulation.8 

Microglia in which Aβ has a direct interaction expresses a range of

Berkeley Pharma Tech Journal of Medicine | 17

https://pubmed.ncbi.nlm.nih.gov/24493463/#:~:text=The%20soluble%20building%20blocks%20of,%2Denriched%20microtubule%2Dassociated%20protein.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463297/
https://www.frontiersin.org/articles/10.3389/fncel.2018.00488/full
https://www.frontiersin.org/articles/10.3389/fncel.2018.00488/full
https://www.mdpi.com/2073-4409/11/21/3421
https://www.mdpi.com/2073-4409/11/21/3421


structurally diverse molecules, including TREM2, CD33, CD35, etc.8 

These receptors are responsible for recognition and response to Aβ.8

2.1.4 Current target genes

APOE4: This gene variant is a risk factor for Alzheimer’s disease. APOE 
expression produces a protein that helps move cholesterol in the 
bloodstream.9 While the exact mechanism of APOE4 is not fully known, 
di�culties with a brain cell’s ability to process fats may play an important 
role in Alzheimer's disease.

APP: This gene encodes amyloid precursor protein, the precursor for 
amyloid-B peptides.10 The cleavage of APP forms amyloid beta plaques 
which aggregate in the brain in AD.

PSEN1 and PSEN2: These genes encode for a large component of the 
protein y-secretase, which is responsible for splicing and processing of APP 
to form amyloid B peptides.11 The accumulation of amyloid beta plaques is 
prominently seen in those with AD.

TREM2: (Triggering Receptor Expressed on Myeloid cells 2): This gene 
provides instruction for a cell surface receptor found on microglia, immune 
cells in the brain. Variations in TREM2 have been associated with an 
increased risk of developing AD. TREM2 is responsible for various 
functions in microglia including cell survival, phagocytosis, etc.12 Reports 
indicate that TREM2 de�ciency results in the decreased presence of 
microglia around Aβ plaques.12 Due to the plethora of mutations within the 
TREM2 gene resulting in the progression of AD, precision medicine can 
help target speci�c genetic subgroups. By catering to these speci�c TREM2 
mutations, a more e�ective treatment plan can be constructed.

2.1.5 Current treatments for Alzheimer’s Disease

The current treatments for Alzheimer’s include cholinesterase inhibitors 
(Donepezil and Galantamine), antipsychotics (Brexpiprazole), and 
disease-modifying immunotherapies (Lecanemab and Aducanumab).13 

Besides the immunotherapies, these medications address the symptoms of 
Alzheimer’s Disease rather than attacking the disease at its source. 
Meanwhile, the immunotherapies help remove amyloid plaques, but do not

Berkeley Pharma Tech Journal of Medicine | 18

https://www.mdpi.com/2073-4409/11/21/3421
https://www.mdpi.com/2073-4409/11/21/3421
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463297/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453386/
https://pubmed.ncbi.nlm.nih.gov/24927704/#:~:text=Presenilin%201%20(PSEN1)%20and%20presenilin,formation%20of%20amyloid%2D%CE%B2%20peptides.
https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-018-0247-7
https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-018-0247-7
https://www.nia.nih.gov/health/how-alzheimers-disease-treated


stop the plaques from accumulating or the amyloids from forming. As 
revealed by extensive research, the pathophysiology of AD is incredibly 
nuanced with various factors. Current treatments are not a cure-all; more 
targeted treatments personalized to the root causes for each patient are 
necessary for prevention and mitigation.

2.2 Schizophrenia

Schizophrenia, unlike neurodegenerative diseases like Alzheimer’s disease, is 
a neurological disorder commonly known as a mental illness impacting how 
a person acts, feels, and behaves, thus not only a�ecting themselves, but also 
the individual’s relationships with those around them.14 Coined by Eugen 
Bleuler in 1908, schizophrenia in more professional terms is a functional 
psychotic disorder characterized by the experience of delusional beliefs, 
hallucinations, and disturbances in thought, perception, and behavior.15 

Schizophrenia can be diagnosed through classi�cation systems, of which the 
Diagnostic and Statistical Manual of Mental Disorders 4 (DSM-4) and 
International Classi�cation of Diseases (ICD-10) are most commonly used. 
For the DSM-4:

Two or more of the following symptoms must be present for a 
signi�cant portion of time during a one-month period16:

● Delusions

● Hallucinations

● Disorganized speech

● Grossly disorganized or catatonic behavior

● Negative symptoms.

There must also be social/occupational dysfunction. Continued negative
symptoms and disturbances must last for at least six months, with at least 1
month of active-phase symptoms described above. On the other hand, the
ICD-10 has sub-categories for schizophrenia based on presenting
symptoms:

Berkeley Pharma Tech Journal of Medicine | 19

https://www.nimh.nih.gov/health/topics/schizophrenia
https://www.ncbi.nlm.nih.gov/books/NBK539864/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181977/


One of the following symptoms, for a period greater than or equal
to a month:

● Thought insertion, echo, broadcast, or withdrawal

● Delusions of control, in�uence, or passivity

● Hallucinatory voices providing a running commentary of
the patient

● Persistent delusions that are culturally inappropriate or
implausible

Or, at least two of the following symptoms for a period greater than 
or equal to a month16:

● Persistent hallucinations in any modality when
accompanied by �eeting delusions

● Breaks of interpolations in thought resulting in
incoherence or neologisms

● Catatonic behavior

● Negative symptoms

● Signi�cant and consistent transformation in the overall
quality of behavior manifesting as anhedonia and social
withdrawal

These detailed criteria allow for further characterizing schizophrenia into 
paranoid schizophrenia, hebephrenic schizophrenia, catatonic 
schizophrenia, undi�erentiated schizophrenia, post-schizophrenic 
depression, residual schizophrenia, and simple schizophrenia.16 

Schizophrenic symptoms can be classi�ed as positive symptoms, including 
hallucinations, delusions, and formal thought disorders, and negative 
symptoms such as anhedonia, poverty of speech, and lack of motivation.15

2.2.1 Pathophysiology

Berkeley Pharma Tech Journal of Medicine | 20

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181977/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181977/
https://www.ncbi.nlm.nih.gov/books/NBK539864/


The neurochemical abnormality hypothesis credits imbalance in 
dopaminergic, serotonergic, and alpha-adrenergic hyperactivity or 
glutaminergic and GABA hypoactivity.15 Another hypothesis includes the 
involvement of the four main dopaminergic pathways with the highs 
resulting from hyperactive D2 receptors via the mesolimbic pathway. This 
theory also attributes motor symptoms to low dopamine levels in the 
nigrostriatal pathway due to how the extrapyramidal system is a�ected.15 

Reduced mesocortical dopamine levels in the mesocortical pathway result in 
negative symptoms.17 Research has demonstrated the exacerbation of 
positive and negative symptoms in schizophrenia from NMDA receptor 
antagonists, shining light on the potential role of glutamatergic 
hypoactivity.18 Neuroanatomically, a ventricle enlargement and reduction of 
gray matter volume is typical in patients with schizophrenia.17

The genes neuregulin (NGR1) and dysbindin (DTNBP1), which are 
involved in glutamate signaling and glutamate release, have been implicated 
respectively, as well as a gene polymorphism that regulates dopamine 
function known as catecholamine O-methyltransferase (COMT).15 Higher 
levels of the immune protein C4 are also linked to an increased risk of 
developing the condition.19 Interestingly, other factors such as advanced 
paternal age and the association with auto-immune diseases have been 
recent epidemiological �ndings for increased risk of schizophrenia.20

2.2.2. Current treatments for Schizophrenia

Mainstream medications for schizophrenia include an oral 
second-generation antipsychotic (SGA) such as aripiprazole, olanzapine, 
risperidone, quetiapine, asenapine, lurasidone, sertindole, ziprasidone, 
brexpiprazole, molindone, iloperidone, etc.14 Benzodiazepines such as 
diazepam, clonazepam, or lorazepam may also be prescribed to control 
behavioral disturbances and non-acute anxiety.14 Apart from medication, 
cognitive behavioral therapy (CBT) can be used to address anxiety, 
depression, speech disabilities, and psychosis.14 However, while these 
medications aim to target speci�c neurotransmitters or certain symptoms, 
they fail to target the root issues that may emerge in di�erent ways for each 
patient. With multiple di�erent factors, neurological conditions such as 
schizophrenia cannot be addressed with a blanket solution. Advances in

Berkeley Pharma Tech Journal of Medicine | 21

https://www.ncbi.nlm.nih.gov/books/NBK539864/
https://www.ncbi.nlm.nih.gov/books/NBK539864/
https://www.nature.com/articles/mp201247
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159061/
https://www.nature.com/articles/mp201247
https://www.ncbi.nlm.nih.gov/books/NBK539864/
https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(22)00551-3
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727721/
https://www.nimh.nih.gov/health/topics/schizophrenia
https://www.nimh.nih.gov/health/topics/schizophrenia
https://www.nimh.nih.gov/health/topics/schizophrenia


research uncovering schizophrenia pathophysiology reveal modulated
receptors and neurotransmitters as possible targets for precision medicine
through various methods, such as gene editing, pharmacogenomics, and
iPSC models.

3. Precision Medicine

Precision medicine (PM) stands as a transformative paradigm, especially in 
neurology where diseases can exhibit dynamic and ever-changing 
characteristics. Neurogenetic disease, in�uenced by the diverse genetic, 
environmental, and stochastic factors, eventually leads to aberrant biological 
pathways that unfold at varying rates. This variability is further 
compounded by compensation mechanisms, resulting in subtle changes in 
physiological functions and behavioral performance. In the realm of 
neurology, PM has the potential to revolutionize healthcare by shifting the 
focus from diagnostic work-ups and therapeutic interventions after clinical 
manifestation to proactive prevention and health prolongation serving as a 
screener, changing expectations toward prevention, and prolonging health.21

It should be recognized that current applications have limitations in regard 
to diversity that exists within the human genome. Future integration of 
genome databases that re�ect the global population could change how 
precision medicine is administered universally and remove some of the 
barriers that currently exist within the �eld.21 Rather than intervening 
therapeutically only when diseases manifest clinically, PM enables 
time-sensitive detection and diagnosis. Treatment strategies can be tailored 
based on an individual's unique clinical, genetic, and biological 
characteristics, minimizing the risk and cost of unnecessary medical 
interventions, as demonstrated in Figure 2. Molecular changes, often the 
target of treatment, can be speci�cally addressed through PM, providing a 
more e�ective and e�cient healthcare approach.

The proposed work�ow for PM in neurology involves a comprehensive 
approach to data collection, integration, and clinical decision-making.22 

System biology and systems neurophysiology serve as major data sources, 
incorporating information from various modalities, including MRI, PET, 
genomics, cytomics, and proteomics. Digitally enabled data collection

Berkeley Pharma Tech Journal of Medicine | 22

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086532/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086532/
https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(22)00258-2#:~:text=Precision%20medicine%20(PM)%20approaches%20in,biological%20characteristics%20and%20risk%20factors


systems and large-scale population genomic analyses, such as genome-wide
association studies (GWAS), contribute to a holistic understanding of
neurological diseases and are part of the model. Digital Data, GWAS,
Systems Biology, and Systems Neurophysiology are then integrated using
the three key steps–data generation, data integration, and clinical
approach–that form the foundation of PM in neurology. AI plays a crucial
role in facilitating time-dependent analysis, longitudinal tracking, and
clinical decision-making, addressing the complexity and diversity of
neurological diseases. By analyzing this data on a population scale,
researchers can identify patterns, correlations, and genetic markers
associated with neurological diseases. This comprehensive approach allows
for a deeper understanding of the complex interplay between genetics,
environment, and disease manifestation. Moreover, it enables researchers to
uncover potential biomarkers, risk factors, and novel therapeutic targets,
thus providing a more holistic view of neurological disorders beyond just
their symptoms or genetic components.

The data system operates by collecting, storing, and analyzing vast amounts
of genomic and clinical data from diverse populations. Through
sophisticated algorithms and analytical techniques, researchers can identify
genetic variants associated with neurological diseases, understand their
underlying mechanisms, and predict disease risk in individuals. This
knowledge can inform personalized treatment approaches tailored to a
patient's genetic pro�le, lifestyle, and environmental factors, leading to
more e�ective diagnoses and treatment plans for neurological conditions.

Berkeley Pharma Tech Journal of Medicine | 23



Figure 2. A diagram showing how precision medicine di�ers from traditional medicine by 
designing treatment plans that are individualized to target the speci�c patient. The use of 
general procedures versus targeted treatments is at the discretion of the physician and the 
availability of treatment plans for that particular patient, As the �eld advances, targeted 
treatment plans are expected to be more prevalent, providing a more holistic approach to 
addressing neurological disease.

4. Challenges and Limitations of Precision Medicine

Despite the promises of PM, there are notable challenges and limitations. 
“Black box” medicine refers to untransparent computational models in 
healthcare decision-making.23 Traditional approaches rely on explicit 
understanding of biological mechanisms such as through clinical trials, 
whereas “black box” medicine utilizes large-scale datasets and sophisticated 
algorithms to uncover complex and often hidden relationships among 
multiple patient characteristics.   Unlike traditional personalized medicine, 
which relies on explicit understanding of simple relationships, “black box” 
medicine delves into intricate networks of variables, such as observable 
factors like age and sex, as well as less obvious ones like genomic markers. 
“Black box” medicine represents a shift towards leveraging the power of big 
data and advanced algorithms to improve healthcare outcomes, but it 
requires careful navigation of technical, ethical, and regulatory complexities.

Berkeley Pharma Tech Journal of Medicine | 24

https://jolt.law.harvard.edu/articles/pdf/v28/28HarvJLTech419.pdf


First, the “black box” issue in the underlying AI models raises immense 
concerns about the lack of transparency and understanding of model 
outputs.23 Current AI approaches may reveal systems complexities without 
elucidating the underlying reasons, making interpretation and clinical 
decision-making di�cult. Data standardization and curation challenges can 
also arise, particularly in large-scale, multimodal data collection and 
monitoring.

Addressing the complexities of algorithms in precision medicine necessitates 
a multifaceted approach. Transparency and interpretability are crucial for 
understanding algorithmic decisions, even in black-box systems. Rigorous 
validation and evaluation procedures ensure reliability and e�ectiveness, 
while ethical considerations guide fair and equitable outcomes. Regulatory 
oversight, continual monitoring, and interdisciplinary collaboration further 
enhance algorithmic development and deployment. By navigating these 
challenges thoughtfully, stakeholders can harness the potential of algorithms 
to advance precision medicine while safeguarding patient interests and 
promoting public health.23

Additionally, the transition from gene-gene association analyses to 
multi-omics analyses in systems biology poses di�culties that must be 
addressed for the e�ective implementation of PM in neurology.23 

Furthermore, the successful implementation of precision medicine 
encounters several other hurdles, encompassing ethical considerations, the 
impact of stigma, and potential issues related to cost-e�ectiveness. Ethical 
components crucial to the correct application of precision medicine involve 
con�dentiality and privacy concerns, particularly regarding the analysis of 
massive datasets.24 This requires the development of a robust ethical-legal 
framework to ensure secure data sharing. Both public and self-stigma could 
in�uence the acceptance of precision medicine, potentially a�ecting public 
health policies and patient participation.24 The problem of cost-e�ectiveness 
in precision medicine lies at the intersection of evolving medical 
technologies and economic evaluations. While precision medicine holds the 
promise of tailoring treatments to individual patients, the economic 
viability of these interventions faces multifaceted challenges. Economic 
evaluations, typically assessing the cost per quality-adjusted life year (QALY) 
gained, encounter di�culties in capturing the true value of precision

Berkeley Pharma Tech Journal of Medicine | 25

https://jolt.law.harvard.edu/articles/pdf/v28/28HarvJLTech419.pdf
https://jolt.law.harvard.edu/articles/pdf/v28/28HarvJLTech419.pdf
https://jolt.law.harvard.edu/articles/pdf/v28/28HarvJLTech419.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186890/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186890/


medicine.25 The scarcity of robust clinical and cost data, particularly in 
real-world settings, poses a signi�cant hurdle. Additionally, the lack of 
standardized willingness-to-pay thresholds and the varying perspectives 
adopted in economic analyses contribute to the ambiguity surrounding the 
cost-e�ectiveness of precision medicine.25 This all raises questions about the 
long-term sustainability of these approaches in public healthcare.

5. Speci�c strategies and methods

5.1 iPSC

With rapid and advanced-paced technology, new avenues have opened to 
treating neurogenetics disorders with stem cell treatment. For example, 
induced pluripotent stem cells (iPSC) are a type of stem cell derived from 
adult cells that have the potential to develop into di�erent types of cells in 
the body.26 These cells are created through a process called reprogramming 
which involves the introduction of speci�c genes into a specialized cell to 
reprogram it back to a state similar to that of an embryonic stem cell. 
Because these iPSCs are derived from the patients themselves, genetic 
information and characteristics unique to the individual can be transferred 
to the newly reprogrammed stem cell. By personalizing therapies, scientists 
can work toward creating treatments targeting speci�c underlying causes. 
An ongoing clinical trial derives iPSCs from somatic cells from individuals 
with neurological disease in hopes of creating a line of cells for modeling 
diseases and drug discovery.27

5.1.1 Alzheimer’s Disease (AD)

Studies show iPSCs have enormous potential for treating neurological 
diseases such as Alzheimer’s Disease and Schizophrenia.28 In one study 
iPSCs derived from autologous, mouse skin �broblasts injected into 
subiculum resulted in the decrease of alpha beta plaques deposition and 
beta/gamma secretase activity. These mouse models have immense impact 
in understanding the underlying mechanisms for AD; however, while mice 
are evolutionarily similar to humans, stark di�erences remain due to only 
50% of microglial genes being identical between the two species.29 Due to 
such limitations of modeling age-related neurodegenerative aspects of AD 
in dividing cells of mice, ongoing e�orts focus on optimizing protocols for

Berkeley Pharma Tech Journal of Medicine | 26

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867980/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867980/
https://www.intechopen.com/chapters/85399
https://clinicaltrials.gov/study/NCT00874783?cond=Alzheimers%20Disease&intr=iPSC&rank=1
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869146/#:~:text=A%20number%20of%20studies%20demonstrated,into%20glial%20cells%20upon%20implantation
https://www.nature.com/articles/s41380-019-0468-3


the creation of induced pluripotent stem cells (iPSCs) tailored for human 
applications.

5.1.2 Schizophrenia

One study used human induced pluripotent stem cells (hiPSC) from 
individuals with high genetic risk for schizophrenia and those without, and 
found di�erences in how these cells behaved and functioned in people with 
schizophrenia. These di�erences in cell behavior matched some of the main 
symptoms seen in people with schizophrenia.30 The identi�cation of 
neurophysiological measures via hiPSC associated with the patient’s 
personal clinical characteristics is signi�cant for generating novel 
therapeutics.

5.2 Genetic Pro�ling

Genetic pro�ling involves studying an individual's DNA to identify speci�c 
variations (mutations or polymorphisms) in genes associated with 
neurological disorders.31 Identifying speci�c genetic variations associated 
with the disease allows for personalized risk assessment.

5.2.1 Alzheimer’s Disease

Speci�c genetic variations associated with Alzheimer's risk or progression 
can provide valuable information about a person's susceptibility to 
Alzheimer's and their risk of developing the disease, allowing for a 
personalized approach to treating the neurodegenerative disease. For 
example, certain variations in genes like APOE and mutations within the 
PS-1, PS-2, and APP genes are known to increase the risk of developing 
Alzheimer's in families with multiple individuals a�ected by AD. Studying 
these variations helps estimate an individual's likelihood of developing 
Alzheimer's based on their genetic makeup, allowing for implementation of 
proactive measures and lifestyle changes that may help reduce the risk or 
delay the onset of Alzheimer's. An example of this approach can be seen 
through genetic linkage analysis, where the researchers investigated the 
in�uence of the APOE, APP, PS1, and PS-2 genes on the increased risk of 
AD in families where multiple individuals were already diagnosed with the 
disease.32

Berkeley Pharma Tech Journal of Medicine | 27

https://www.pnas.org/doi/epdf/10.1073/pnas.2109395119
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157398/
https://clinicaltrials.gov/study/NCT05010603?cond=Alzheimers%20Disease&intr=Genetic%20Testing&rank=3


5.2.2 Schizophrenia

Schizophrenia is believed to have a complex genetic component.33 By 
studying an individual's genetic makeup, researchers aim to identify speci�c 
genetic markers or variations that may increase the risk of developing 
schizophrenia. This information can be used to provide personalized risk 
assessments, allowing for early preventative measures. One study used RNA 
sequencing (LCM-seq) on a speci�c area called the granule cell layer in the 
hippocampus, which is important for memory.34 This area mainly has a type 
of brain cell called granule neurons, and they make up a small part of the 
whole hippocampus. Problems with these neurons have been linked to 
conditions like bipolar disorder and schizophrenia. The results posed a clear 
picture of which gene variants pose a risk for schizophrenia compared to 
more general methods.

5.3 Pharmacogenomics

Pharmacogenomics involves studying how an individual's genetic makeup 
in�uences their response to medications.35 Genetic variations can a�ect how 
drugs are absorbed, metabolized, and utilized in the body. Tailoring drug 
choices maximizes e�ectiveness and minimizes side e�ects. This method 
helps identify drugs that may not be well-tolerated by a speci�c individual 
due to their unique genetic makeup.

5.3.1 Alzheimer’s Disease

In the context of Alzheimer's, pharmacogenetics is crucial for optimizing 
medication selection and dosages. Studies have shown how an AD patient’s 
biological response to drugs depends on speci�c gene clusters that in�uence 
how drugs are received in the body.36 Pharmacogenetic research indicates 
that the e�ectiveness of drug therapies for Alzheimer's Disease (AD) varies 
depending on genetic makeup, which is closely linked to gene clusters 
associated with pharmacogenetic processes. In the course of the study, a 
signi�cant proportion of AD cases exhibit an accumulation of 15 to 26 
defective pharmagenes, a�ecting the metabolism of drugs through enzymes. 
Pharmacogenetics holds promise in enhancing drug development and 
maximizing the e�ectiveness of available therapeutic options for AD by 
optimizing patient care and therapeutic outcomes.37

Berkeley Pharma Tech Journal of Medicine | 28

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433970/
https://www.nature.com/articles/s41593-020-0604-z
https://www.nigms.nih.gov/education/fact-sheets/Pages/pharmacogenomics.aspx#:~:text=Pharmacogenomics%20(sometimes%20called%20pharmacogenetics)%20is,or%20she%20responds%20to%20medications.
https://www.alz.org/alzheimers-dementia/treatments/medications-for-memory
https://link.springer.com/protocol/10.1007/978-1-0716-2573-6_13#Abs1


Leveraging pharmacogenetics can enhance the e�ciency of drug 
development and maximize the constrained therapeutic resources dedicated 
to Alzheimer's disease (AD). This approach enables the personalized 
utilization of anti-dementia medications, both independently and in 
combination with other drugs tailored to address concurrent disorders.

5.3.2 Schizophrenia

Schizophrenia can be treated through utilizing pharmacogenomics to 
analyze how genetic variations in�uence an individual's response to 
medications commonly used to treat the disease, such as antipsychotic 
drugs. This enables the selection of drugs and dosages that are most e�ective 
while minimizing potential side e�ects. While antipsychotics are the main 
treatment for Schizophrenia, many have adverse reactions towards these 
medications and the alternative is to use a trial and error method to �nd an 
e�ective treatment plan. The drawbacks to this are delays in treatment and 
overall worsening the disease condition. One study aimed to research the 
therapeutic e�cacy of multigenic pharmacogenomics-guided treatment in 
patients with schizophrenia. The results displayed that patients treated with 
MPCT had greater symptom improvement than their counterpart, patients 
treated with the standard 6-week treatment. This highlights the e�ectiveness 
of pharmacogenomics as a potential treatment plan for those with 
schizophrenia.38

6. Conclusion/Future Directions

Precision medicine is the future to address neurological diseases due to 
addressing the genetic variance in patients that cause similar symptoms but 
require di�erent treatment plans. Personalized care through a variety of 
treatment options that are based on the patient’s genetic pro�le provides an 
opportunity to drastically improve their quality of life by treating the disease 
on a molecular level rather than only the symptoms. Currently, the 
accessibility and cost of precision medicine are limiting factors for it to be a 
realistic treatment plan for the masses. However, as the �eld continues to 
advance through continued research in pharmacogenomics, metabolomics, 
and novel treatments such as iPSCs, precision can become normalized as a

Berkeley Pharma Tech Journal of Medicine | 29

https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2810261


more e�ective strategy to cure neurological diseases, and costs will
presumably be reduced as the technology becomes more widespread.

Berkeley Pharma Tech Journal of Medicine | 30



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