Cerebrospinal fluid biomarkers and rate of cognitive decline in very mild dementia of the Alzheimer type.
BACKGROUND
Cerebrospinal fluid (CSF) levels of Abeta peptide 1-42 (Abeta 42), tau, and phosphorylated tau (ptau) are potential biomarkers of Alzheimer disease.


OBJECTIVE
To determine whether Abeta 42, tau, and ptau predict the rate of cognitive change in individuals with very mild dementia of the Alzheimer type (DAT).


METHODS
Retrospective analysis of CSF biomarkers and clinical data.


METHODS
An academic Alzheimer disease research center.


METHODS
Research volunteers in a longitudinal study of aging and cognition. Participants (n = 49) had a clinical diagnosis of very mild DAT with a Clinical Dementia Rating (CDR) of 0.5 at the time of lumbar puncture. All the participants had at least 1 follow-up assessment (mean [SD] follow-up, 3.5 [1.8] years).


METHODS
Baseline CSF levels of Abeta 42, Abeta 40, tau, and ptau at threonine 181 (ptau181) and the rate of dementia progression as measured using the CDR sum of boxes (CDR-SB) score and psychometric performance.


RESULTS
The rate of dementia progression was significantly more rapid in individuals with lower baseline CSF Abeta 42 levels, higher tau or ptau181 levels, or high tau: Abeta 42 ratios. For example, the annual change in the CDR-SB score was 1.1 for the lowest 2 tertiles of Abeta 42 values and 0.3 for the highest tertile of Abeta 42 values.


CONCLUSIONS
In individuals with very mild DAT, lower CSF Abeta 42 levels, high tau or ptau181 levels, or high tau:Abeta 42 ratios quantitatively predict more rapid progression of cognitive deficits and dementia. Biomarkers of CSF may be useful prognostically and to identify individuals who are more likely to progress for participation in therapeutic clinical trials.
Snider
Barbara J
BJ
Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 S Euclid, St Louis, MO 63110, USA. sniderj@neuro.wustl.edu
Fagan
Anne M
AM
Roe
Catherine
C
Shah
Aarti R
AR
Grant
Elizabeth A
EA
Xiong
Chengjie
C
Morris
John C
JC
Holtzman
David M
DM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000503:physiopathology* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000503:physiopathology* / Q000523:psychology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000032:analysis / Q000134:cerebrospinal fluid*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D016875:tau Proteins / Q000032:analysis / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins