8 modules on Alzheimer’s disease: amyloid biochemistry, tau pathology, the genetics of APOE/APP/PSEN1, biomarker-led diagnosis (CSF, amyloid PET, plasma p-tau217), and the modern era of anti-amyloid therapy (lecanemab, donanemab, ARIA management).
Eight Modules
- Part I — Overview & Epidemiology: Alois Alzheimer 1906 case of Auguste Deter, ~55M people with dementia globally (~70% AD), projected 139M by 2050, biological NIA-AA 2018 ATN definition.
- Part II — Neuroanatomy: Hippocampus and entorhinal cortex, default-mode network, Braak tau staging I-VI, Thal amyloid phasing 1-5, locus coeruleus pretangle hypothesis, glymphatic clearance during sleep.
- Part III — Amyloid Cascade: Hardy & Higgins 1992, APP processing (α / β-secretase / γ-secretase), Aβ42:Aβ40 ratio, oligomer-toxicity hypothesis, plaques as endpoint not driver. PDB: Aβ NMR, BACE1 + inhibitor.
- Part IV — Tau & Tauopathy: MAPT gene, 3R/4R isoforms, hyperphosphorylation, paired helical filaments, the six cryo-EM tau folds (Goedert/Scheres 2017), prion-like spread, plasma p-tau biomarkers. PDB: 5O3L, 6HRE.
- Part V — Genetics: Familial AD (APP, PSEN1, PSEN2), Down syndrome and APP triplication, the APOE-ε4 allele dose response (1 copy ~3x, 2 copies ~12x), TREM2 R47H, GWAS pathway groupings. PDB: APOE3, TREM2.
- Part VI — Diagnosis: NIA-AA 2018 biological framework, ATN classification, CSF Aβ42/p-tau, amyloid PET (PiB, florbetapir, Centiloid scale), tau PET, plasma p-tau217 revolution, MRI volumetry, FDG-PET.
- Part VII — Therapy: Cholinesterase inhibitors, memantine, the anti-amyloid antibody arc (bapineuzumab→solanezumab→aducanumab→lecanemab→donanemab), CLARITY-AD and TRAILBLAZER-ALZ-2 readouts, ARIA-E/H, anti-tau pipeline.
- Part VIII — Prevention & Future: Lancet Commission 14 modifiable factors (~45% preventable), FINGER trial, SPRINT-MIND, ACHIEVE hearing-aids trial (48% reduction in 3-yr decline), GLP-1 agonists in cognitive trials.
The therapy module is built around the 2023–2024 inflection point: lecanemab and donanemab are the first interventions to meaningfully slow clinical AD progression, with 27% and 35% slowing on the CDR-Sum-of-Boxes respectively.