Is amyloid-β harmful to the brain? Insights from human imaging studies

Although the amyloid-β protein associated with the Alzheimer’s disease plaque has been detectable in living people for over a decade, its importance in the pathogenesis of Alzheimer’s disease is still debated. The frequent presence of amyloid-β in the brains of cognitively healthy older people has been interpreted as evidence against a causative role. If amyloid-β is crucial to the development of Alzheimer’s disease, it should be associated with other Alzheimer’s disease-like neurological changes. This review examines whether amyloid-β is associated with other biomarkers indicative of early Alzheimer’s disease in normal older people. The preponderance of evidence links amyloid-β to functional change, progressive brain atrophy, and cognitive decline. Individuals at greatest risk of decline seem to be those with evidence of both amyloid-β and findings suggestive of neurodegeneration. The crucial question is thus how amyloid-β is related to brain degeneration and how these two processes interact to cause cognitive decline and dementia. The presence of β-amyloid in the brain may represent a preclinical stage of Alzheimer’s disease, but this is controversial. Jagust examines the association between β-amyloid and biomarkers of Alzheimer’s disease in cognitively normal older people, concluding that β-amyloid is harmful to the brain in a manner consistent with Alzheimer’s disease.