Educational scope notice: This is a study note for medical students, not medical advice, diagnosis, or treatment guidance. Clinical management should follow local protocols and current guidelines.
Cerebral amyloid angiopathy is a disease of ageing. Sporadic disease usually appears from the fifth decade onward. Moderate-to-severe vessel pathology is found in about one quarter of the general elderly population at autopsy. That figure comes from cohorts with a mean age near 85, so it does not describe prevalence at age 60.
MRI sees only part of the disease. In Alzheimer cohorts, pathology prevalence is roughly double the rate of strictly lobar microbleeds on MRI (48% versus 22%). In the general population the gap is roughly threefold (23% versus 7%). Microbleeds on MRI likely identify only severe vessel disease.
Pre-test probability follows the bleed location. About half of lobar haemorrhages are driven by amyloid angiopathy, by pathology (57%) and by Boston-criteria diagnosis (about 50%). In unselected intracerebral haemorrhage the share is roughly one fifth to one quarter. In cognitively normal older adults, moderate-to-severe vessel pathology affects about 6%.
APOE genotype separates two steps of the disease. The epsilon-4 allele increases amyloid deposition in vessel walls and brings the first lobar haemorrhage forward by roughly 5 years. The epsilon-2 allele instead raises the risk of bleeding from vessels already loaded with amyloid, through destructive wall changes such as fibrinoid necrosis. Epsilon-2 is not protective overall.
Hereditary forms
Hereditary forms are rare and autosomal dominant, usually caused by APP gene mutations. They begin earlier and run a more severe course than sporadic disease. The Dutch type (APP E693Q) is the best studied. Carriers develop recurrent strokes in the fifth and sixth decades. Stroke is often the first sign and is fatal in about one third. Survivors commonly develop dementia, and about half of those with strokes develop recurrent seizures. Far rarer non-APP forms include Icelandic (cystatin C) and British/Danish (ITM2B) disease.
Evidence anchors
- Jakel et al. 2022, prevalence of cerebral amyloid angiopathy systematic review and meta-analysis: https://pmc.ncbi.nlm.nih.gov/articles/PMC9290643/
- Greenberg et al. 1996, apolipoprotein E epsilon-4 and the clinical course of cerebral amyloid angiopathy: https://www.ahajournals.org/doi/10.1161/01.STR.27.8.1333
- Nicoll et al. 2000, APOE genotype and cerebral amyloid angiopathy-related haemorrhage: https://pubmed.ncbi.nlm.nih.gov/10818505/
- Biffi 2022, main features of hereditary cerebral amyloid angiopathies systematic review: https://pmc.ncbi.nlm.nih.gov/articles/PMC9616336/
- MedlinePlus Genetics, hereditary cerebral amyloid angiopathy: https://medlineplus.gov/genetics/condition/hereditary-cerebral-amyloid-angiopathy
- ALZFORUM, APP E693Q Dutch-type mutation record: https://www.alzforum.org/mutations/app-e693q-dutch