Cerebrospinal fluid beta-amyloid(1-42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease.
OBJECTIVE
To study the diagnostic potential of the 42 amino acid form of beta-amyloid (beta-amyloid(1-42)) in cerebrospinal fluid (CSF) as a biochemical marker for Alzheimer disease (AD), the intra-individual biological variation of CSF-beta-amyloid(1-42) level in patients with AD, and the possible effects of differential binding between beta-amyloid and apolipoprotein E isoforms on CSF-beta-amyloid(1-42) levels.


METHODS
A 20-month prospective follow-up study.


METHODS
Community population-based sample of consecutive patients with AD referred to the Piteå River Valley Hospital, Piteå, Sweden.


METHODS
Fifty-three patients with AD (mean +/- SD age, 71.4 +/- 7.4 years) diagnosed according to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria and 21 healthy, age-matched (mean +/- SD age, 68.8 +/- 8.0 years) control subjects.


METHODS
Cerebrospinal fluid beta-amyloid(1-42) level--analyzed using enzyme-linked immunosorbent assay--and severity of dementia--analyzed using the Mini-Mental State Examination.


RESULTS
Mean +/- SD levels of CSF-beta-amyloid(1-42) were decreased (P<.001) in patients with AD (709 +/- 304 pg/mL) compared with controls (1678 +/- 436 pg/mL). Most patients with AD (49 [92%] of 53 patients) had reduced levels (<1130 pg/mL). A highly significant correlation (r = 0.90; P<.001) between baseline and 1-year follow-up CSF-beta-amyloid(1-42) levels was found. There were no significant correlations between CSF-beta-amyloid(1-42) level and duration (r = -0.16) or severity (r = -0.02) of dementia. Low levels were also found in patients with mild dementia (Mini-Mental State Examination score, >25).


CONCLUSIONS
The sensitivity of CSF-beta-amyloid(1-42) level as a diagnostic marker for AD is high. The intra-individual biological variation in CSF-beta-amyloid(1-42) level is low. Low CSF-beta-amyloid(1-42) levels are also found in the earlier stages of dementia in patients with AD. These findings suggest that CSF-beta-amyloid(1-42) analyses may be of value in the clinical diagnosis of AD, especially in the early course of the disease, when drug therapy may have the greatest potential of being effective but clinical diagnosis is particularly difficult.
Andreasen
N
N
Department of Rehabilitation, Piteå River Valley Hospital, Sweden. niels.andreasen@nll.se
Hesse
C
C
Davidsson
P
P
Minthon
L
L
Wallin
A
A
Winblad
B
B
Vanderstichele
H
H
Vanmechelen
E
E
Blennow
K
K
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003704:Dementia / Q000134:cerebrospinal fluid; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008487:Medical History Taking; D011237:Predictive Value of Tests; D011446:Prospective Studies; D020033:Protein Isoforms / Q000235:genetics; D012016:Reference Values; D012044:Regression Analysis; D013997:Time Factors
D016229:Amyloid beta-Peptides; D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D015415:Biomarkers; D020033:Protein Isoforms