Alzheimer’s Disease
Alzheimer’s Disease — Neurodegeneration up Close
From amyloid biochemistry and tau pathology to lecanemab and prevention — eight integrating modules.
Why a course on Alzheimer’s?
Alzheimer’s disease (AD) accounts for roughly two-thirds of the ~55 million people living with dementiaworldwide; that number is projected to triple by 2050. AD is the 7th-leading cause of death globally and the most expensive disease per patient-yearin many high-income countries due to long-term care.
Despite a century of work since Alois Alzheimer’s 1906 case report on Auguste Deter, the disease has only recently entered the era of disease-modifying therapy. The 2023 approval of lecanemab and 2024 approval of donanemab — both anti-amyloid monoclonals — marked the first interventions that meaningfully slow clinical progression. The course traces the biology, the diagnostic revolution of biomarkers, and the open frontier of tau- and inflammation-targeted therapy. It cross-references Neuroscience, Cell Physiology, Pharmacology, and Stroke.
Course Parts
Overview & Epidemiology
Definitions, dementia spectrum, ~55 M people with dementia globally, ~70% of which is AD; demographic projections, the cost of care, the disease as the largest neurological burden of the coming decades.
Neuroanatomy of AD
Entorhinal cortex → hippocampus → temporoparietal → frontal: the canonical Braak staging trajectory. The default-mode network. Why memory is hit first.
Amyloid Cascade
Aβ peptide generation: APP processing, β- and γ-secretase, Aβ42:Aβ40 ratio, oligomers vs plaques, the Hardy-Selkoe hypothesis and its 30-year evolution.
Tau & Tauopathy
Tau hyperphosphorylation, paired helical filaments, neurofibrillary tangles. Why tau correlates better with cognitive decline than amyloid.
Genetics & Risk Factors
Autosomal-dominant familial AD (APP, PSEN1, PSEN2). The APOE-ε4 allele — risk and dose response. TREM2, CR1, CLU, and the genome-wide picture.
Diagnosis & Biomarkers
Clinical criteria (NIA-AA 2018, ATN), CSF Aβ42/p-tau, amyloid PET (PiB, florbetapir), tau PET, blood biomarkers (p-tau217), volumetric MRI.
Therapy
Cholinesterase inhibitors, memantine, anti-amyloid monoclonals (aducanumab, lecanemab, donanemab) and the ARIA-E/H controversy, anti-tau therapy in development.
Prevention & Future
Lifestyle (FINGER trial), midlife BP/diabetes, the SPRINT-MIND result, sleep & glymphatic clearance, exercise, cognitive reserve. Drug pipelines beyond amyloid.
What you’ll learn
- Distinguish AD clinically from other dementias (LBD, FTD, vascular, mixed).
- Trace APP processing through α-, β-, and γ-secretase to Aβ peptides.
- Reason about why oligomers, not plaques, may be the toxic species.
- Predict APOE-ε4 dose effect on lifetime risk.
- Read CSF and amyloid-PET biomarker reports under the ATN framework.
- Anticipate ARIA-E/H risk in patients on anti-amyloid antibodies.
- Counsel a patient on the FINGER lifestyle bundle.
- Critically evaluate the amyloid hypothesis after 30 years.
Prerequisites
Working knowledge of CNS anatomy, basic biochemistry of proteostasis, and membrane-protein processing. The course cross-references Neuroscience, Cell Physiology, and Biochemistry.