Why has there been so little progress on Alzheimer's disease?

Amyloid Hypothesis, Fraud, and Gatekeeping

• Many comments blame decades of focus on β‑amyloid plaques (especially Abeta 42) for crowding out alternative ideas.
• Allegations of image fabrication and “foundational” fraud are seen as having distorted funding, publication, and diagnostic criteria (“plaque cartel”).
• Others argue the amyloid model is likely incomplete rather than outright wrong: plaques correlate with pathology, some mutations clearly increase amyloid, and early anti‑amyloid drugs may slow progression if used pre‑symptomatically.
• Gatekeeping by a small expert elite is blamed for grant control, peer‑review hostility to dissenting work, and “monoculture” in research agendas, even without bad intent.
• Some push back that experts are often right and that the scientific system, while flawed, isn’t fundamentally “broken.”

Inherent Difficulty and Heterogeneity

• The brain is hard to study (no easy biopsy, limited imaging), Alzheimer’s progresses slowly, and early stages are hard to detect.
• Definitive diagnosis still requires autopsy; many people have plaques without symptoms and vice versa.
• Several commenters stress Alzheimer’s is not a single disease but a heterogeneous set of age‑related neurodegenerative conditions.
• Comparisons are made to cancers and schizophrenia: many overlapping mechanisms, systems-level dysregulation rather than a single cause.

Alternative and Complementary Theories

• Viral/infectious hypotheses (notably herpesviruses, shingles) and epidemiologic links with vaccines and antivirals are discussed as promising but not definitive.
• Metabolic views frame Alzheimer’s as “type‑3 diabetes” or glucose transport failure in the brain; energy shortage, endocrine decline, and cardiovascular issues are emphasized.
• Other proposed contributors: gum disease and oral bacteria, gut microbiome, chronic inflammation, trauma and high ACE scores, sleep and glymphatic failure, lifestyle and social isolation, and genetics (APP, presenilin, APOE).
• Low‑dose lithium and various supplements are mentioned, with mixed personal reports and acknowledgment that evidence is early or unclear.

Funding, Pharma, and Regulation

• Alzheimer’s is described as relatively well funded compared to conditions like ME/CFS or long COVID; disease funding overall is seen as misaligned with burden and quality‑of‑life loss.
• Some criticize pharma as structurally biased toward long‑term treatments; others respond that companies will pursue any truly effective therapy, including cures.
• The FDA is alternately criticized as too risk‑averse in general and too permissive specifically in Alzheimer’s (approving expensive drugs with weak clinical benefit and serious side effects).

Prevention, Aging, and Outlook

• A major theme is that dementia risk is strongly age‑linked; commenters argue aging biology itself is underfunded relative to Alzheimer’s.
• Multi-factor prevention (exercise, diet, social engagement, sleep, vascular health) is highlighted; one Lancet estimate of ~45% preventable cases is cited via a commercial prevention program.
• Overall sentiment: fraud and gatekeeping likely delayed progress, but the core problem remains that Alzheimer’s reflects a deeply complex, multi‑factor failure of aging brain systems.