For decades, neurology has told us that Alzheimer’s disease is caused by toxic proteins (amyloid plaques and tau tangles) that clog the brain. Pharmaceutical companies have poured billions into anti-amyloid drugs designed to wash them away. The results? Repeated failures, high-profile disappointments, and a handful of marginal approvals with no meaningful improvement in patients’ lives. Sound familiar? In cardiology, we’ve built an entire industry on lowering LDL cholesterol. Statins move the lab numbers impressively, yet the absolute benefit is modest: in primary prevention, maybe a 1 to 2 percent absolute risk reduction in events over five to 10 years, with an NNT often in the 50 to 100 range.
Now look at what happens when you target the likely cause rather than the downstream debris. In 2017, a nationwide Taiwanese study followed more than 33,000 patients with HSV infection. Those who did not receive antivirals had a dementia incidence of about 28.8 percent over ten years. Those treated with anti-herpetic drugs (acyclovir, valacyclovir, and famciclovir) had an incidence of just 2.9 percent.
- Absolute risk reduction (ARR): A reduction of 25.9 percent.
- Number needed to treat (NNT): Approximately four.
For every four HSV patients treated, one case of dementia was prevented over ten years. That’s staggering. Compare it to statins: NNT approximately 50 to 100 in primary prevention. Here, NNT is approximately four. The signal is so strong that skeptics argue it must be confounding, but even if only partly true, the magnitude suggests we’ve been looking in the wrong place.
Which brings us back to amyloid and tau. Instead of “toxic junk,” these proteins may be the brain’s version of a granuloma: defensive structures spun out to wall off microbes. Autopsies of Alzheimer’s brains have revealed herpesviruses, Chlamydia pneumoniae, spirochetes, fungi, and periodontal bacteria like Porphyromonas gingivalis. Different organisms, same pattern: persistent infection, chronic immune activation, and walling-off responses that eventually destroy host tissue.
We’ve seen this before. In TB, granulomas protect but scar lungs. In reactive arthritis, antibiotics improve outcomes because they hit the driver, not just the inflammation. In cardiology, arterial plaques may also be granulomas, walling off pathogens like C. pneumoniae. A recent Japanese study found its DNA in every single plaque sampled. And yet we keep lowering numbers: LDL, amyloid PET scans, and Lp(a). We polish the smoke while ignoring the fire.
Granulomas in TB. Amyloid plaques in Alzheimer’s. Atherosclerotic plaques in heart disease. Even reactive arthritis joints. Different tissues, different outcomes, but perhaps the same story: infection sparking a maladaptive immune response that medicine mistakes for the disease itself.
It’s time to stop pretending biomarker reduction is victory. We need the trial neurology has avoided: a randomized antiviral study in early Alzheimer’s. And cardiology needs the same courage: a randomized antimicrobial trial in younger patients with early atherosclerosis, using a triple-drug regimen for at least six months. Past antibiotic trials failed because they gave one drug for a week to patients already too far gone. That’s like giving two aspirin to someone with metastatic cancer and declaring the drug class useless. If plaques are infectious granulomas, we need to treat them with the same seriousness infectious disease doctors already use for TB, leprosy, and HIV. Until then, we’ll keep congratulating ourselves for moving numbers while leaving patients to suffer the same outcomes.
Larry Kaskel is an internist and “lipidologist in recovery” who has been practicing medicine for more than thirty-five years. He operates a concierge practice in the Chicago area and serves on the teaching faculty at the Northwestern University Feinberg School of Medicine. In addition, he is affiliated with Northwestern Lake Forest Hospital.
Before podcasts entered mainstream culture, Dr. Kaskel hosted Lipid Luminations on ReachMD, where he produced a library of more than four hundred programs featuring leading voices in cardiology, lipidology, and preventive medicine.
He is the author of Dr. Kaskel’s Living in Wellness, Volume One: Let Food Be Thy Medicine, works that combine evidence-based medical practice with accessible strategies for improving healthspan. His current projects focus on reevaluating the cholesterol hypothesis and investigating the infectious origins of atherosclerosis. More information is available at larrykaskel.com.
