Low Cerebrospinal Fluid Aβ(42) and Aβ(40) are Related to White Matter Lesions in Cognitively Normal Elderly

BACKGROUND: Low cerebrospinal fluid (CSF) levels of Aβ(42) may be the earliest manifestation of Alzheimer’s disease (AD). Knowledge on how CSF Aβ interacts with different brain pathologies early in the disease process is limited. We examined how CSF Aβ markers relate to brain atrophy and white matter lesions (WMLs) in octogenarians with and without dementia to explore the earliest pathogenetic pathways of AD in the oldest old. OBJECTIVE: To study CSF amyloid biomarkers in relation to brain atrophy and WMLs in 85-year-olds with and without dementia. METHODS: 53 octogenarians took part in neuropsychiatric examinations and underwent both a lumbar puncture and a brain CT scan. CSF levels of Aβ(42) and Aβ(40) were examined in relation to cerebral atrophy and WMLs. Dementia was diagnosed. RESULTS: In 85-year-olds without dementia, lower levels of both CSF Aβ(42) and CSF Aβ(40) were associated with WMLs. CSF Aβ(42) also correlated with measures of central atrophy, but not with cortical atrophy. In participants with dementia, lower CSF levels of Aβ(42) were related to frontal, temporal, and parietal cortical atrophy but not to WMLs. CONCLUSIONS: Our findings may suggest that there is an interrelationship between Aβ and subcortical WMLs in older persons without dementia. After onset of dementia, low CSF Aβ(42), probably representing amyloid deposition in plaques, is associated with cortical atrophy. WMLs may be an earlier manifestation of Aβ deposition than cortical degeneration.