Alzheimer's disease is the most common cause of dementia worldwide. Its pathological hallmarks are amyloid plaques (extracellular deposits of beta-amyloid peptide) and neurofibrillary tangles (intracellular aggregates of hyperphosphorylated tau protein). These accumulate over decades, beginning long before symptoms appear, and the structural casualty list begins with the hippocampus.
The early hippocampal damage explains the clinical signature. Patients first lose recent memory. They cannot remember what they did this morning, the conversation they just had, the new acquaintance's name. Remote memories — childhood, early adulthood, decades-old material — remain accessible, sometimes vividly. The new books cannot be filed; the old books remain on the shelves.
As the disease progresses and pathology spreads through the cortex, even the old books begin to disappear. Long-term memories of family, of one's profession, of one's own life narrative gradually fade. Language fails. Recognition of familiar faces falters. The patient who remembered their wedding day in vivid detail now cannot recognize their spouse. The library that had been intact in the early years is slowly being emptied.
One of the more important neurochemical features of Alzheimer's is the early loss of cholinergic neurons in the basal forebrain. These neurons supply acetylcholine to the cortex and hippocampus, and acetylcholine is essential for memory consolidation and attention. As they die, the surviving cortex is starved of the modulator it needs to encode new information.
This is the rationale for cholinesterase inhibitors — donepezil, rivastigmine, galantamine — as treatment. They block the enzyme that degrades acetylcholine, preserving the remaining cholinergic signal as the basal forebrain depopulates. The effect is modest but real: a few months to a year of slower cognitive decline in many patients. Memantine, an NMDA receptor modulator, adds a small additional benefit in moderate-to-severe disease.
Recent years have brought disease-modifying treatments to market — lecanemab and donanemab are monoclonal antibodies that clear amyloid plaques from the brain. They produce measurable slowing of decline in early disease, but they carry risk (ARIA — amyloid-related imaging abnormalities) and the magnitude of clinical benefit is debated. The therapeutic landscape is shifting; the underlying clinical reality of the patient losing their librarian over years remains the same.
When you next encounter an early Alzheimer's patient, picture the hippocampus depopulating. The recent books are not getting filed. The old shelves are still there, for now. And then, eventually, the library itself begins to empty.