Apolipoprotein E in cerebrospinal fluid in 85-year-old subjects. Relation to dementia, apolipoprotein E polymorphism, cerebral atrophy, and white matter lesions
I. Skoog, C. Hesse, P. Fredman, L. A. Andreasson, B. Palmertz and K. Blennow
Department of Psychiatry, Sahlgrenska Hospital, Goteborg, Sweden.
OBJECTIVE: To further elucidate the pathogenetic role of apolipoprotein E
(Apo E) in degenerative brain disorders, we analyzed cerebrospinal fluid
(CSF) levels of Apo E in 85-year-old subjects with dementia disorders.
DESIGN: Survey. SETTING: Community. PARTICIPANTS: Population-based sample
of 27 demented (12 with Alzheimer disease [AD]; 13, vascular dementia
[VAD]; and 2, other types of dementia) and 35 nondemented individuals. MAIN
OUTCOME MEASURES: Cerebrospinal fluid levels of Apo E, Apo E polymorphism,
and brain atrophy and white matter lesions (WMLs) measured by computed
tomography (CT) of the brain. Dementia was defined according to Diagnostic
and Statistical Manual of Mental Disorders, Third Edition, Revised
criteria; AD, National Institute of Neurological and Communicative
Disorders and Stroke and the Alzheimer's Disease and Related Disorders
Association criteria; and VAD, National Institute of Neurological Disorders
and Stroke and the Association Internationale pour la Recherche et
l'Enseignement en Neuroscience criteria. RESULTS: The mean (+/- SD) CSF
levels of Apo E were lower in the AD (2.6 +/- 1.5 mg/L; P < .02) and VAD
groups (2.5 +/- 0.9 mg/L; P < .002) than in the nondemented group (3.8
+/- 1.7 mg/L). Cerebrospinal fluid levels of Apo E decreased with
increasing severity of dementia and with increasing temporal cortical and
central frontal atrophy. In nondemented individuals, CSF levels of Apo E
decreased with increasing degree of WMLs. Cerebrospinal fluid levels of Apo
E were not influenced by the Apo E4 isoform. CONCLUSIONS: Whether our
finding of an association between low CSF levels of Apo E and dementia
disorders (both degenerative, such as AD, and vascular, such as VAD) is
related to the pathogenesis of these disorders or is a secondary
consequence of the disease process remains to be established. Although
statistical correlations do not give direct evidence of causal relations,
the correlations between CSF level of Apo E and severity of dementia and
cortical atrophy suggest that CSF level of Apo E follows the disease
process.
