Mutations that increase amyloid production (APP, PSEN1/2) and the extra APP copy in Down syndrome reliably produce early-onset Alzheimer’s, implying amyloid sits upstream in the disease process. This genetic evidence outweighs weak plaque–symptom correlations and mouse-model anomalies. The A→T→N chain provides a coherent causal story for timing and pathology.
— It elevates genetics as the causal standard for contested biomedical debates, shaping drug evaluation and research priorities.
BeauHD
2025.10.16
60% relevant
The study’s rapid, 45% amyloid‑beta reduction and reversal of cognitive deficits after BBB repair bolster the view that amyloid sits upstream in AD pathology and that clearing it improves function, aligning with the genetics‑driven amyloid‑first causal chain.
msmash
2025.10.09
82% relevant
Whitney carries a deterministic early‑onset AD mutation yet remains healthy with heavy amyloid but minimal tau, aligning with the A→T→N causal chain (amyloid upstream of tau and neurodegeneration) and highlighting a protective bottleneck between amyloid and tau that the Washington University study (Nature Medicine) characterizes.
Scott Alexander
2025.08.14
100% relevant
Down syndrome (trisomy 21) raises APP dosage and amyloid levels, with two-thirds developing Alzheimer’s by 60; dozens of APP/PSEN mutations cause similarly early disease.