Biochemical markers in persons with preclinical familial Alzheimer disease.

June 3, 2008 Nursing
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Biochemical markers in persons with preclinical familial Alzheimer disease.

Neurology. 2008 May 28;

Authors: Ringman JM, Younkin SG, Pratico D, Seltzer W, Cole GM, Geschwind DH, Rodriguez-Agudelo Y, Schaffer B, Fein J, Sokolow S, Rosario ER, Gylys KH, Varpetian A, Medina LD, Cummings JL

BACKGROUND: Persons at risk for familial Alzheimer disease (FAD) provide a model in which biomarkers can be studied in presymptomatic disease. METHODS: Twenty-one subjects at risk for presenilin-1 (n = 17) or amyloid precursor protein (n = 4) mutations underwent evaluation with the Clinical Dementia Rating (CDR) scale. We obtained plasma from all subjects and CSF from 11. Plasma (Abeta40, Abeta42, F2-isoprostanes) and CSF (F2-isoprostanes, t-tau, p-tau181, Abeta40, Abeta42, and Abeta42/Abeta40 ratio) levels were compared between FAD mutation carriers (MCs) and noncarriers (NCs). RESULTS: Plasma Abeta42 levels (25.1 pM vs 15.5 pM, p = 0.031) and the ratio of Abeta42/Abeta40 (0.16 vs 0.11, p = 0.045) were higher in presymptomatic MCs. Among MCs, those with CDR scores of 0.5 had lower plasma Abeta42 levels than those with CDR scores of 0 (14.1 pM vs 25.1, p = 0.02). The ratio of Abeta42 to Abeta40 was also reduced in the CSF (0.08 vs 0.15, p = 0.046) of nondemented MCs compared to NCs. Total CSF tau and p-tau181 levels were elevated in presymptomatic FAD MCs. CSF levels of F2-isoprostanes were also elevated in MCs (n = 7, 48.6 pg/mL) compared to NCs (n = 4, 21.6 pg/mL, p = 0.031). CONCLUSIONS: Our data indicate that Abeta42 is elevated in plasma in familial Alzheimer disease (FAD) mutation carriers (MCs) and suggests that this level may decrease with disease progression prior to the development of overt dementia. We also demonstrated that the ratio of Abeta42 to Abeta40 was reduced in the CSF of nondemented MCs and that elevations of t-tau and p-tau181 are sensitive indicators of presymptomatic disease. Our finding of elevated F2-isoprostane levels in the CSF of preclinical FAD MCs suggests that oxidative stress occurs downstream to mismetabolism of amyloid precursor protein.

PMID: 18509095 [PubMed - as supplied by publisher]

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June 3, 2008 | Filed Under Nursing 

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