ALZHEIMER’S

Old protein-trash brain

Alzheimer’s Disease is a proteopathic dementia. “Proteopathic” means protein folding disease. The mechanism is incompletely understood. We think the cause is accumulation of a proteinaceous trash called Amyloid. We think that a receptor in the brain called APP stops being broken down, and accumulated APP will morph into big clumps of junk called amyloid. Piles of amyloid, called amyloid plaques, accumulate outside of cells. These stinky trash piles somehow damage the nearby healthy brain tissue. In neurons, it causes the structural beams (tau proteins) to collapse into “tau tangles.” Alzheimer’s patients also have a deficiency in acetylcholine, which is made in the basal nucleus of Meynert (not clear if this is a cause or consequence of the disease). Alzheimer’s accounts for the majority of dementia. There is a lot of new exciting research in the field. 

Risk factors?

The biggest risk factor is poor cardiovascular health (hypertension, obesity, diabetes). There are hundreds of genes that modify the risk of Alzheimer’s (literally hundreds). A genetic mutation in the ApoE2 enzyme causes early-onset “familial” Alzheimer’s. Trisomy 21 also greatly increases Alzheimer’s disease, likely because the nasty APP protein is encoded by the 21st chromosome.

Typical symptoms?

Insidious onset in an old person. Memory loss precedes personality changes. Short term memory goes first, then long term memory. It’s like their memory gradually rewinds back towards childhood.

Diagnosis?

Clinical. If you did get a CT or MRI, you would see diffuse cortical atrophy. There are fancy new immunotherapy-guided imaging techniques, but these aren’t ready for primetime yet.

Treatment?

Not much available. A supportive family is important. There are two classes of medications that subtly improve symptoms, but they are of dubious efficacy and don’t slow disease progression. Donepezil (acetylcholinesterase inhibitor) is the first line, and Memantine (NMDA blocker) is for moderate-to-severe cases.