Plasma amyloid beta-protein and C-reactive protein in relation to the rate of progression of Alzheimer disease.
OBJECTIVE
To examine whether plasma markers of amyloid precursor protein metabolism (amyloid beta-protein ending in Val-40 [Abeta40] and Ala-42 [Abeta42]), inflammation (high-sensitivity C-reactive protein), and folic acid metabolism (folic acid, vitamin B(12), and total homocysteine levels) are associated with the rate of cognitive and functional decline in persons with Alzheimer disease.


METHODS
Longitudinal study across a mean (SD) of 4.2 (2.6) years with assessments at approximately 6- to 12-month intervals.


METHODS
Outpatient care.


METHODS
A cohort of 122 patients having a clinical diagnosis of probable Alzheimer disease, each with at least 2 assessments across time.


METHODS
Scores on the cognitive Information-Memory-Concentration subscale of the Blessed Dementia Scale and the functional Weintraub Activities of Daily Living Scale.


RESULTS
Low plasma levels of Abeta40, Abeta42, and high-sensitivity C-reactive protein were associated with a significantly more rapid cognitive decline, as indexed using the Blessed Dementia Scale, than were high levels. Low levels of Abeta42 and high-sensitivity C-reactive protein were significantly associated with more rapid functional decline on the Weintraub Activities of Daily Living Scale than were high levels. These plasma markers contributed about 5% to 12% of the variance accounted for on the Blessed Dementia Scale and the Activities of Daily Living Scale by fixed-effects predictors. Measures of folic acid metabolism were not associated with changes on either the Blessed Dementia Scale or the Activities of Daily Living Scale.


CONCLUSIONS
Plasma markers of amyloid precursor protein metabolism and C-reactive protein may be associated with the rate of cognitive and functional decline in patients with Alzheimer disease.
Massachusetts Alzheimer's Disease Research Center, Wang Ambulatory Care Center, Suite 720, Room 731-G, Massachusetts General Hospital, 15 Parkman St, Boston, MA 02114, USA. jlocascio@partners.org
Joseph J
JJ
Locascio
Hiroaki
H
Fukumoto
Liang
L
Yap
Teodoro
T
Bottiglieri
John H
JH
Growdon
Bradley T
BT
Hyman
Michael C
MC
Irizarry
D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C500436:amyloid beta-peptide (5-40); C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D002097:C-Reactive Protein