Ep. 32: Revolutionizing Alzheimer’s Diagnosis — with Dr. Winnie Pak, Neuroscientist

The disease people fear most isn’t cancer or even heart disease — it’s Alzheimer’s. In this episode, Dr. Regina Druz talks with neuroscientist Dr. Winnie Pak about a quiet revolution in how Alzheimer’s is detected: the pathology can be present in the brain up to twenty years before the first symptom, and we can now see it. They unpack the two hallmarks of the disease — amyloid plaques and tau tangles — and why tau, especially its ability to ‘spread,’ is far more deterministic than amyloid alone. Along the way they explore APOE4 and genetics, the Lancet Commission’s fourteen modifiable risk factors, the landmark US POINTER lifestyle study, and a new blood assay that mirrors a tau PET scan — all framed by a truth Dr. Druz returns to again and again: the heart and brain share the same vascular roots, so what’s good for the heart is great for the brain.

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Episode Chapters

[00:00] Introduction & the Heart-Brain Connection
[04:04] Meet Dr. Winnie Pak: A Neuroscientist’s Path
[06:50] Crossing to Drug Development & Rare Disease
[10:50] Why the Needle Hasn’t Moved on Alzheimer’s
[14:30] Pathology Decades Before Symptoms: Amyloid
[16:40] Amyloid vs. Tau: Risk Factor vs. Determinant
[19:00] APOE4, Lifestyle & the Lancet’s 14 Risk Factors
[23:18] What Tau Is, and Why Spreading Matters
[28:50] Tau PET, Blood Tests & the 3-to-5-Year Window
[35:30] US POINTER, Drugs & the Case for Early Detection
[44:00] The VeraBIND Tau Assay: Catching the Inflection Point
[55:17] Who Should Test? Risk Tolerance & Closing

Transcript

[00:00] Introduction & the Heart-Brain Connection

Dr. Regina Druz (00:02): Welcome to Own Your Heart Health. I’m Dr. Regina Druz, your holistic cardiologist. This week we’ll dive into common heart health concerns, uncovering root causes and unpacking scientific discoveries and controversies. The information provided does not constitute medical advice. Please contact your healthcare practitioner before making any changes that may impact your health.

Dr. Regina Druz (00:40): Hi everyone. I’m super excited about today’s guest, someone who opened my eyes to extraordinary new opportunities in preventing one of the most dreaded diseases in our society — and no, not cancer, and not even heart disease, but Alzheimer’s disease. My guest is Dr. Winnie Pak, who has a deep footprint in neuroscience and clinical strategy. She currently heads medical affairs for a company breaking new ground in testing for Alzheimer’s-type dementia, bringing tremendous expertise in neuroscience and the execution of complex phase-three trials — bridging scientific rigor with practical implementation. Welcome, Winnie.

Dr. Winnie Pak (02:01): Thank you so much, Regina. It’s so nice to be here. Most of the time my hat is medical affairs — education, going out and speaking with people interested in this topic. A lot of what people hear is sometimes decades-old information, yet we’ve made huge strides, even in the last couple of years; the diagnostic tools around now, most people haven’t even heard of. I’m so happy to join.

Dr. Regina Druz (02:40): As a cardiologist, we always think about the brain, the kidneys — that’s part of the cardiology universe. But when I became an integrative and functional medicine physician, I realized the common root causes driving heart disease, cancer, and Alzheimer’s overlap so much it’s almost impossible to talk about one without the others. The heart-brain connection is extraordinary, and at its core it’s vascular. We even do home-based testing we call our Heart and Brain Toolkit. So let me ask what I ask every guest: how did you grow up to be a neuroscientist?

[04:04] Meet Dr. Winnie Pak: A Neuroscientist’s Path

Dr. Winnie Pak (04:04): It’s a convoluted path. For undergrad I did biochemistry and psychology — interested in both. Around the same time my grandmother developed what we called Alzheimer’s, though back in the late ’90s and early 2000s there really wasn’t a diagnosis in life; it was confirmed only post-mortem, when you’d see the plaques. What we knew was her cognition was going downhill, with hallucinations and the agitation that can come with dementia, and eventually she went into a nursing home because my grandfather couldn’t care for her. That made me ask, what is happening to grandma? I loved psychology and the pathophysiology of disease — so why not combine them? I got my PhD in neuroscience at UC San Diego and did a postdoctoral fellowship at the Salk Institute.

Dr. Regina Druz (06:08): Then you wanted the application of that knowledge.

Dr. Winnie Pak (06:20): Exactly. I loved basic science — discovering something new is its own reward — but something was missing: the translation from basic science into clinical science, where society actually benefits. So I went into industry, on the drug-development side.

[06:50] Crossing to Drug Development & Rare Disease

Dr. Regina Druz (06:50): Or, as they say, you crossed to the dark side.

Dr. Winnie Pak (07:00): My advisor was against it — at the time UC San Diego had the number-one neuroscience program, and the attitude was, why waste that pedigree on industry? But that translational pull was strong. I’d interned at Genentech multiple summers as an undergrad and loved it. That was over 20 years ago. There wasn’t much in Alzheimer’s then, so I worked in Parkinson’s — on a drug for Parkinson’s psychosis that’s now approved — and then in rare diseases, which opened my eyes to giving a voice to people who don’t have one. Then a company approached me to head medical affairs for Alzheimer’s, and it came full circle — back to my grandmother. Alzheimer’s has always been in my heart.

Dr. Regina Druz (10:00): That’s your purpose. I can relate — on my mom’s side many relatives lived into their 90s and 100s (my great-grandmother was 102), but several also had Alzheimer’s-type dementia. As a clinician, my bread and butter is seeing patients in a holistic, integrative way, and some come to us with mild cognitive impairment or an Alzheimer’s diagnosis. Yet despite enormous research, we haven’t meaningfully moved the needle. Why?

[10:50] Why the Needle Hasn’t Moved on Alzheimer’s

Dr. Winnie Pak (10:55): That’s the point — the needle isn’t moving quickly, partly from decades of inertia. Back when my grandmother had it, there was no real in-life diagnosis, and physicians were trained with that in mind: what’s the purpose of diagnosing when there’s no treatment? That bias against diagnosing still lingers. And frontline primary-care physicians, who see most of these patients, were never trained to recognize the early forms of neurodegenerative disease — so when someone says, ‘Doc, something’s not quite right,’ it gets waved off as normal aging. We need to be able to recognize and stratify: is this normal aging, or is there something to follow up on?

Dr. Winnie Pak (14:04): Because this is a progressive disease, ‘let’s just keep an eye on it’ means that by next year’s checkup the person can be very different — the pathology of Alzheimer’s can be present for about 20 years before symptoms show up.

[14:30] Pathology Decades Before Symptoms: Amyloid

Dr. Regina Druz (14:30): Tell us about that — it shook my world. Twenty years before symptoms? That’s scary.

Dr. Winnie Pak (14:45): It’s a lot like cardiology: plaques are in your arteries for a long time before a heart attack or stroke. I always say what’s good for the heart is great for the brain — we’re one machine; keep it tuned up and it takes care of us. The two hallmarks of Alzheimer’s are amyloid plaque, which most people have heard of, and tau tangles. We learned early that we can identify amyloid in the brain at least 20 years before clinical symptoms. The first in-life diagnostic was the amyloid PET scan — before that it was post-mortem only — and then came cerebrospinal fluid testing, which is more invasive (a lumbar puncture). Both give definitive answers that amyloid is present.

Dr. Winnie Pak (16:09): But here’s the key: as much as amyloid is an absolute hallmark, it’s more of a risk factor — a huge one, and you do need to be amyloid-positive for a diagnosis of Alzheimer’s — but it isn’t deterministic on its own.

[16:40] Amyloid vs. Tau: Risk Factor vs. Determinant

Dr. Regina Druz (16:46): In cardiology, hypertension, dyslipidemia, and smoking are powerful risk factors — but not everyone with them develops clinical disease; many have stable, subclinical plaque. So how accurate is amyloid for forecasting that someone will actually develop cognitive impairment?

Dr. Winnie Pak (17:20): It depends — nature and nurture. On the genetic side, the best-known factor is the APOE4 allele, which you in cardiology have tested for far longer than neurology has. One copy makes someone about three times more likely to develop Alzheimer’s; two copies, up to roughly fifteen times — but it’s still not fully penetrant. There are rare presenilin mutations that nearly guarantee it, but in the general population APOE4 is the major recognized factor, and the most common allele, APOE3, leaves most people at baseline risk.

[19:00] APOE4, Lifestyle & the Lancet’s 14 Risk Factors

Dr. Winnie Pak (19:10): And the nurture side is what’s good for the heart is great for the brain — exercise, sleep, keeping blood pressure and A1c in check. Some centenarians actually have amyloid in their brains yet stay sharp; they have resilience factors science hasn’t fully identified. The Lancet Commission on dementia prevention, updated last year, identified fourteen modifiable risk factors that together could prevent nearly half of dementia cases — not trivial. They only included factors with robust evidence: addressing hearing, for instance, accounts for a meaningful share, and education and staying curious build resilience. So finding amyloid is not a guarantee of symptoms. What’s becoming clear is that tau is a much more deterministic factor.

Dr. Regina Druz (23:00): So what is tau, and how does it differ from amyloid?

[23:18] What Tau Is, and Why Spreading Matters

Dr. Winnie Pak (23:30): Both are normal proteins with important jobs. Amyloid is normally upregulated under trauma or stress — that’s fine. The problem is when it misfolds and becomes sticky: the brain can’t clear it, so it sequesters the clumps into plaques and tucks them away, like hiding clutter in a closet when company comes. Tau is different — it’s inside the cell, part of the microtubule scaffolding and the transport system. When tau misfolds and gets hyperphosphorylated, it stops doing its job and forms tangles; the cell tries to expel it, and ultimately the neuron dies. Some of that tau gets secreted into cerebrospinal fluid and now, with newer tests, into the blood.

Dr. Regina Druz (28:24): So when phosphorylated tau shows up in the bloodstream, the train has somewhat left the station — the cells have already been damaged and tau is leaking out, even crossing the blood-brain barrier. That’s not a great development.

[28:50] Tau PET, Blood Tests & the 3-to-5-Year Window

Dr. Winnie Pak (28:55): A paper out this summer, using tau PET in a large population, found that once you become tau-PET positive, symptoms appear within about three to five years. People who were cognitively unimpaired transitioned to mild cognitive impairment in that window, and those already at MCI progressed to mild Alzheimer’s. That’s important, because now we have something more deterministic than a risk factor — and three to five years, depending how you look at it, is a short time, but maybe enough to slow progression.

Dr. Winnie Pak (30:50): And the US POINTER study showed that structured lifestyle modification — exercise, better eating, accountability — significantly slowed progression, with no drug at all. We knew taking better care of this machine pays dividends; POINTER gave it scientific rigor. How great would it be if doctors wrote that as a prescription — a lifestyle prescription — with programs and accountability built in, transitioning our sick-care system into true healthcare?

Dr. Regina Druz (34:05): So true. And people assume interventions must be complex, when there’s low-hanging fruit: even adding 1,000 steps a day is associated with a meaningful drop in cardiovascular mortality — often better than medications, without side effects. We cover the new data on mild cognitive impairment, lithium, and the US POINTER study in our monthly Holistic Heartbeat newsletter, which anyone can sign up for from our website.

[35:30] US POINTER, Drugs & the Case for Early Detection

Dr. Regina Druz (35:30): What you’re describing is scary for me — I have a family history of Alzheimer’s — and probably for you too. So what are the new opportunities to detect change before pathology consumes the brain? Amyloid imaging and phosphorylated tau detect damage that’s already happening.

Dr. Winnie Pak (36:00): It’s tough, because science wants to confirm safety before tools reach the public, so most clinics have nothing until symptoms appear, and the phosphorylated-tau blood tests available now are only indicated for symptomatic patients. That makes them more of a disease-activity check — like checking cholesterol after someone already has a stent. They’re meant to be complementary: clinical diagnosis alone is only about two-thirds accurate, so these assays help clinicians be more confident.

Dr. Winnie Pak (38:36): And now there are the first disease-modifying drugs for the mild and early stages — anti-amyloid antibody therapies that slow progression by roughly 30%. Some say that’s nothing; I’ll take 30 over zero. But they carry side effects that become more relevant in later stages, so they’re not indicated once patients reach moderate disease — the benefit-risk ratio shifts. That’s exactly why identifying patients earlier matters: a mildly impaired patient can still act on lifestyle change; a moderately impaired one largely cannot. And there are now secondary-prevention trials enrolling people who are pathology-positive but cognitively unimpaired — even aiming for something like a vaccine someday.

Dr. Regina Druz (43:21): Hi everyone, it’s Dr. Regina here. I know there are contradictory opinions about nutrition for heart health and longevity — the discussion gets heated and confusing. Some push low-fat, low-cholesterol; others are fans of a ketogenic diet; and there are many voices urging vegan or vegetarian eating. To cut through the clutter, my team and I created Holistic Heart University: on-demand courses, nutrition and lifestyle resources, and supplement guidance to make healthy choices for your heart easier to understand. I’m especially proud of our open office hours and the Q&A feature where you can put us in the hot seat. Head to the show notes for the link and use promo code OWNER20 for 20% off our annual subscription. I’ll see you in office hours.

[44:00] The VeraBIND Tau Assay: Catching the Inflection Point

Dr. Regina Druz (44:00): With your company you have a chance to do exactly what we do in cardiology — identify patients who have biological pathology early but are still cognitively unimpaired, in that subclinical stage. Tell us about it.

Dr. Winnie Pak (44:30): It’s a blood test — something patients are comfortable with — and its result recapitulates what a tau PET would tell you. The assay has been validated against tau PET at roughly 95 to 96 percent agreement, and a tau PET is expensive and largely paid out of pocket. Here’s the elegant part: tau first accumulates around the hippocampus and entorhinal cortex, where it can sit a long time without much effect. The trouble starts when it spreads out of the medial temporal lobe into the cortex — that’s the inflection point, when executive function and independence are affected. So the assay takes peripheral blood, pulls down the misfolded tau, and asks one question: is this tau capable of spreading? If it’s just sitting put, it’s not causing havoc. If it’s capable of spreading, symptom onset is likely imminent — giving you that same three-to-five-year window a tau PET would.

Dr. Winnie Pak (50:15): So the power of the assay is to give us that time point — and the options that come with it: lifestyle change, clinical trials, available therapies, planning. It’s not ‘that’s it, send grandma to a nursing home.’

Dr. Regina Druz (51:46): Exactly. We’re bringing this testing into the Heart and Brain pathway at Holistic Heart Centers. It’s extraordinary that in Alzheimer’s we can finally move into a domain where we have a bit of time to execute on prevention — ideally these strategies start young, especially if you know your genetics, but people won’t live under duress, so this helps us act when interventions are most likely to matter.

Dr. Regina Druz (53:40): Hi everyone, it’s Dr. Regina here. Many of my colleagues and I are seeing patients arrive with self-ordered blood tests. When this trend started, I thought it would help — who doesn’t want more access to their health data? But too often self-ordered labs lead to more confusion and frustration: patients come in with a pile of results and are no better off. That’s why we created HeartWell Toolkits — a curated collection of at-home blood and genetic markers focused on heart and brain health that gives you the data you need to make informed, actionable decisions. You can order them at the shop on holisticheartcenters.com — the link is in the show notes. Use code TESTING10 for 10% off and free shipping.

[55:17] Who Should Test? Risk Tolerance & Closing

Dr. Regina Druz (55:17): Knowing things even three to five years ahead is powerful — you can meaningfully shift risk factors in three months. We have great opportunities now with cardiometabolic testing, metabolic flexibility, GLP-1 medications, hormone replacement, and peptides — not Alzheimer’s drugs per se, but they target the underlying risk factors. Let me ask a few rapid questions our listeners are wondering. Would you advise a healthy, middle-aged APOE4 heterozygote — single copy, no cognitive impairment — to get this test?

Dr. Winnie Pak (56:39): I’ll couch every answer with: it depends on the person’s risk tolerance. Some people don’t want to know — I’ve had patients ask us to suppress their APOE result, and we honor that. But an Alzheimer’s Association survey found nearly 80% of Americans do want to know, and would ask for a test if they had access. Personally, as a scientist, more information is always better — it gives me control, I decide how to move forward. That said, some people fall into depression on learning they’re positive, so it has to be balanced. Only move forward if it will truly help that patient take better care of themselves; if they’re not in the right headspace, wait. This is a heavy result, emotionally — not like being told you have the flu.

Dr. Regina Druz (59:30): I deeply respect a patient’s right to champion their care their own way. For me, like you, uncertainty is harder — I’d rather know. And it sounds like a patient already at mild cognitive impairment may benefit a bit less from this kind of early pathology test — though it can still help track whether interventions are working, which the common phosphorylated-tau species (like p-tau217 or p-tau181) do less well, since comorbidities such as chronic kidney disease and even recent anesthesia can shift those biomarkers.

Dr. Winnie Pak (1:02:33): Right — a test that measures the pathology itself gives a better read than a snapshot biomarker that drifts. It’s a semi-quantitative assay: it gives you a number, so as a physician you can help patients see whether their lifestyle changes are actually making a dent. Whether they act on it is their decision, but you can put real structure around it and give them an objective readout.

Dr. Regina Druz (1:03:29): This is an eye-opener — and we’ll have you back next year after we implement it (I’ll probably test myself first, as I do). Thank you so much for coming on Own Your Heart Health; it’s been a delight. Listeners, send us your questions and we’ll pass them to Dr. Pak.

Dr. Winnie Pak (1:04:10): Thank you, Regina, for having me — send your questions my way and I’ll address everything I can. Bye-bye.

Dr. Regina Druz (1:04:30): To the professionals listening: if you’re thinking of launching a cardiometabolic or integrative cardiology program in your practice, we can help. Holistic Heart Centers helps physicians expand into hybrid or concierge services — head to the show notes and click the application link; your intro call is entirely free. Ready to schedule a practice review? Use code DOC10 for 10% off our Practice Power Hour, a 60-minute coaching session. Thank you for tuning in to Own Your Heart Health with Dr. Regina Druz. This podcast is powered by Holistic Heart Centers. If you enjoyed the show, please rate and review us on your favorite platform, and visit holisticheartcenters.com and subscribe to our YouTube channel. See you next week.

Frequently Asked Questions

How early can Alzheimer’s pathology be detected — and how is that possible?

Dr. Pak explains that the underlying pathology of Alzheimer’s can be present in the brain about 20 years before the first clinical symptom. Amyloid plaque can be detected at least two decades early — first with an amyloid PET scan (the original in-life test, after years when diagnosis was only possible post-mortem), then via cerebrospinal fluid (a lumbar puncture), and now increasingly through blood tests. Tau, the other hallmark protein, can also be measured — by tau PET and, newly, by blood assays. The key insight she shares is the parallel to cardiology: just as arterial plaque builds silently for years before a heart attack, Alzheimer’s pathology accumulates long before memory changes appear. This is educational information, not medical advice; testing decisions should be made with a qualified clinician.

What’s the difference between amyloid and tau — and which matters more?

Both are normal brain proteins that become harmful when they misfold. Amyloid sits outside cells; when it misfolds it turns sticky, and the brain sequesters the clumps into plaques. Tau lives inside cells as part of their structural scaffolding and transport system; when it misfolds and becomes hyperphosphorylated, it forms tangles and the neuron eventually dies. Dr. Pak emphasizes that amyloid, while an absolute hallmark and a major risk factor (you must be amyloid-positive for a diagnosis), is not deterministic on its own — some healthy centenarians have amyloid in their brains. Tau is more deterministic, and especially tau’s ability to ‘spread’ from the medial temporal lobe into the cortex, which marks the inflection point when symptoms tend to follow. This is general education, not a diagnosis.

Does having the APOE4 gene mean I’ll get Alzheimer’s?

No. Dr. Pak is clear that APOE4 raises risk but is not destiny: one copy makes someone roughly three times more likely to develop Alzheimer’s, and two copies up to about fifteen times — but it is not fully penetrant, meaning many carriers never develop the disease. (Rare presenilin mutations are far more deterministic, but uncommon.) She and Dr. Druz stress the ‘nurture’ side: exercise, sleep, blood-pressure and blood-sugar control, hearing, and staying mentally engaged all influence outcomes — the Lancet Commission identified fourteen modifiable risk factors that together could prevent nearly half of dementia cases. Whether to learn your APOE status is a personal decision that depends on your risk tolerance; some people prefer not to know. Discuss genetic testing — ideally with genetic counseling — and your results with a qualified clinician.

What can I actually do to lower my risk?

A great deal, according to both. Dr. Pak points to the US POINTER study, which showed that a structured lifestyle program — exercise, better nutrition, and accountability — significantly slowed cognitive decline with no drug involved, giving scientific rigor to what clinicians long suspected. The Lancet Commission’s fourteen modifiable factors (including physical activity, blood-sugar and blood-pressure control, hearing, education, and limiting alcohol) could address roughly 45% of dementia cases. Dr. Druz adds that small steps count — even adding about 1,000 steps a day is linked to lower cardiovascular mortality — and that cardiometabolic optimization overlaps heavily with brain protection, because the heart and brain share vascular roots. None of this is a personalized plan; work with your clinician on what’s right for you.

Show Notes & Resources

Guest: Dr. Winnie Pak, PhD

Dr. Winnie Pak is a neuroscientist (PhD, UC San Diego; postdoctoral fellowship at the Salk Institute) and biopharma leader who currently heads medical affairs for Veravas, a company advancing blood-based testing for Alzheimer’s disease. Over a 20-plus-year career in drug development — spanning Parkinson’s, rare diseases, and now Alzheimer’s — she has specialized in translating rigorous neuroscience into clinical strategy and education, including the execution of complex late-stage clinical trials. Her work focuses on bringing earlier, more accurate Alzheimer’s detection to patients and clinicians.

Veravas — maker of the VeraBIND Tau assay (company and product names transcribed from audio; verify exact branding and URL)

Resources Mentioned in This Episode

Veravas / VeraBIND Tau — a blood-based assay that gauges whether misfolded tau is able to ‘spread,’ reported to agree with tau PET roughly 95–96% of the time (company and product names transcribed from audio; verify exact branding)
Tau PET & CSF/plasma tau — imaging and fluid biomarkers; once tau-PET positive, symptoms tend to appear within ~3–5 years
Amyloid PET — the first in-life test for Alzheimer’s pathology, detectable up to ~20 years before symptoms
Phosphorylated-tau blood tests (p-tau217, p-tau181) — currently indicated for symptomatic patients; results can be affected by comorbidities (e.g., chronic kidney disease) and even recent anesthesia
APOE genotyping — APOE4 raises risk (one copy ~3x; two copies up to ~15x) but is not deterministic; rare presenilin mutations are highly penetrant
Lancet Commission on dementia prevention — 14 modifiable risk factors that together could address ~45% of dementia cases
US POINTER study — structured lifestyle modification shown to slow cognitive decline
HHC Heart & Brain Toolkit / pathway — home-based heart-and-brain testing (Veravas testing being added)
‘Chat with the podcast’ on NotebookLM — Google’s public notebook loaded with OYHH episodes (holisticheartcenters.info/notebook)
Holistic Heart University — on-demand courses and resources (use code OWNER20 for 20% off annual)
HeartWell Toolkits — at-home heart and brain health lab + genetic panels (use code TESTING10 for 10% off and free shipping)
For clinicians: Practice Power Hour coaching with Holistic Heart Centers (use code DOC10 for 10% off)

Holistic Heart Centers

holisticheartcenters.com
HeartWell.ai — AI-powered cardiovascular risk assessment
Address: 55 Bryant Avenue, Suite #6, Roslyn, NY 11576
Phone: 877-511-5166
YouTube: @reginadruzmd
Instagram: @dr.reginadruz
Podcast: Own Your Heart Health — available on Apple Podcasts, Spotify, and all major platforms

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