Prediction of Alzheimer's disease using the CSF Abeta42/Abeta40 ratio in patients with mild cognitive impairment.
Evidence supports an important role for beta-amyloid (Abeta) in the pathogenesis of Alzheimer's disease (AD). Here, we investigate baseline levels of the 40- and 42-amino-acid-long Abeta peptides (Abeta40 and Abeta42) in cerebrospinal fluid (CSF) from a cohort of patients with mild cognitive impairment (MCI, n = 137) in relation to the final diagnosis after 4-6 years of follow-up time. CSF Abeta42 concentration at baseline and the Abeta42/Abeta40 ratio were significantly decreased in the MCI patients who developed AD as compared to cognitively stable MCI patients and MCI patients who developed other forms of dementia (p < 0.001). The baseline levels of Abeta40 were similar in all MCI groups but correlated with change in Mini Mental State Examination scores in converters to AD. The Abeta42/Abeta40 ratio was superior to Abeta42 concentration with regard to identifying incipient AD in MCI (p < 0.05). In conclusion, the data provide further support for the view that amyloid precursor protein metabolism is disturbed in early sporadic AD and points to the usefulness of the Abeta42/Abeta40 ratio as a predictive biomarker for AD.
Hansson
Oskar
O
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Zetterberg
Henrik
H
Buchhave
Peder
P
Andreasson
Ulf
U
Londos
Elisabet
E
Minthon
Lennart
L
Blennow
Kaj
K
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000704:Analysis of Variance; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000134:cerebrospinal fluid*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D011237:Predictive Value of Tests; D012016:Reference Values; D012307:Risk Factors; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)