Neurology & Precision Medicine
Brian
Paquette
DO, MPH · Neurology · Pain Medicine · Public Health
Bridging the gap between cutting-edge genomic science and the patients, families, and clinicians navigating Alzheimer’s disease and the APOE ε4 genotype.
“Knowledge of your genotype is not a sentence — it is a starting point.“
As a neurologist, public health practitioner, and APOE ε4 carrier with a deep family history of dementia, I have dedicated my practice to translating the most current peer-reviewed science into actionable, compassionate guidance — for patients, families, and fellow clinicians alike.
Three Pillars of
Evidence-Based Guidance
Built on peer-reviewed evidence from leading journals in neurology, genetics, and preventive medicine.
Genomic Literacy for APOE4 Carriers
Demystifying what it means to carry one or two copies of the APOE ε4 allele — risk stratification, mechanistic science, and what current literature from Nature Medicine, JAMA Neurology, and Alzheimer’s & Dementia reveals about your trajectory.
Neurology of Mild Cognitive Impairment
Understanding the clinical continuum from subjective cognitive decline through MCI to Alzheimer’s disease. Current diagnostic criteria, biomarker frameworks (CSF, PET, blood-based), and the emerging era of disease-modifying therapies.
Navigation for Patients & Families
Translating clinical complexity into clear, actionable paths forward — from genetic counseling and advance planning to lifestyle interventions with robust evidence bases and how to evaluate clinical trial opportunities.
Understanding APOE4 & Brain Health
The apolipoprotein E gene (APOE) encodes a protein central to lipid transport in the brain. The ApoE4 protein isoform drives earlier and more abundant amyloid pathology, influences tau pathology and microglial responses, and functions less efficiently in lipid transport, synaptic plasticity, glucose metabolism, and cerebrovascular function (Yamazaki et al., Nature Reviews Neurology 2019, DOI). That biology now shapes treatment decisions: the risk of ARIA-E with lecanemab and donanemab rises with the number of ε4 alleles (Honig et al., Alzheimer’s Research & Therapy 2024, DOI; Zimmer et al., JAMA Neurology 2025, DOI).
Critically, APOE ε4 status does not determine destiny. Longitudinal cohort data and emerging interventional evidence suggest meaningful modulation of risk through cardiovascular optimization, metabolic health, sleep quality, cognitive reserve, and targeted pharmacologic strategies — areas this resource rigorously explores.
“All content on this platform is grounded in peer-reviewed evidence and designed for an informed audience — patients, caregivers, and clinicians who demand scientific precision alongside clinical compassion.”
My path has been unconventional by design. Training first as a US Naval Flight Surgeon instilled in me a discipline for high-stakes decision-making under uncertainty — a framework that translates directly to the complex, emotionally charged world of cognitive neurology. A subsequent Master of Public Health broadened my lens from the individual patient to the population: who is at risk, who is underserved, and where evidence-based interventions create the most meaningful impact?
When I learned I carry the APOE ε4 allele, it was not with surprise — my family history had long signaled the possibility. What I found surprising was the profound scarcity of reliable, medically rigorous, compassionately framed resources for people in my position. Most available information oscillates between catastrophizing and false reassurance. There is a better path.
This platform exists to be what I could not find: a clinician-scientist’s evidence-based guide to understanding, monitoring, and meaningfully acting upon APOE ε4 carrier status — free from commercial bias, and written with the nuance this science demands.
Former US Naval Flight Surgeon · Indianapolis, Indiana
Resources for Every
Stakeholder
Whether you are a carrier, a family member in the throes of caregiving, or a fellow clinician — there is a path for you here.
APOE4 Carrier Education
In-depth, peer-reviewed explanations of what your genotype means — and, critically, what it does not mean. Risk stratification, mechanisms, and the current horizon of research.
Resources for Clinicians
Physician conversation guides, a laboratory assessment framework, and a clinical trial evaluation guide for discussing APOE ε4 with patients, interpreting biomarker results, and weighing anti-amyloid therapy.
Family & Caregiver Navigation
Translating the science for those living alongside the disease — from early warning signs and planning tools to understanding the latest FDA-approved treatments and how to evaluate clinical trials.
Evidence-Based Lifestyle Medicine
Rigorous review of interventions — cardiovascular, metabolic, sleep, cognitive reserve, dietary — with effect sizes drawn from the highest-quality cohort and interventional data available.
You Do Not Have to Navigate This Alone
Whether you have just received your genetic results or have spent years searching for clear answers, this resource is built for you. Start with the free foundational articles, or join APOE4 Insights Premium for full clinical reviews and graded evidence tables.
APOE4 Insights
Our Approach · All Articles · Become a Member · Donate · Contact · Privacy
© 2026 APOE4 Insights