Distinct pools of beta-amyloid in Alzheimer disease-affected brain: a clinicopathologic study.
OBJECTIVE
To determine whether beta-amyloid (Abeta) peptides segregated into distinct biochemical compartments would differentially correlate with clinical severity of Alzheimer disease (AD).


METHODS
Clinicopathologic correlation study.


METHODS
Twenty-seven patients from a longitudinal study of AD and 13 age- and sex-matched controls without a known history of cognitive impairment or dementia were included in this study.


METHODS
Temporal and cingulate neocortex were processed using a 4-step extraction, yielding biochemical fractions that are hypothesized to be enriched with proteins from distinct anatomical compartments: TRIS (extracellular soluble), Triton (intracellular soluble), sodium dodecyl sulfate (SDS) (membrane associated), and formic acid (extracellular insoluble). Levels of Abeta(40) and Abeta(42) were quantified in each biochemical compartment by enzyme-linked immunosorbent assay.


RESULTS
The Abeta(42) level in all biochemical compartments was significantly elevated in patients with AD vs controls (P < .01). The Abeta(40) levels in the TRIS and formic acid fractions were elevated in patients with AD (temporal, P < .01; cingulate, P = .03); however, Triton and SDS Abeta(40) levels were similar in patients with AD and in controls. Functional impairment proximal to death correlated with Triton Abeta(42) (r = 0.48, P = .02) and SDS Abeta(42) (r = 0.41, P = .04) in the temporal cortex. Faster cognitive decline was associated with elevated temporal SDS Abeta(42) levels (P < .001), whereas slower decline was associated with elevated cingulate formic acid Abeta(42) and SDS Abeta(42) levels (P = .02 and P = .01, respectively).


CONCLUSIONS
Intracellular and membrane-associated Abeta, especially Abeta(42) in the temporal neocortex, may be more closely related to AD symptoms than other measured Abeta species.
Steinerman
Joshua R
JR
Departments of Neurology, Columbia University Medical Center, 630 W 168th St, P&S Box 16, New York, NY 10032, USA.
Irizarry
Michael
M
Scarmeas
Nikolaos
N
Raju
Susan
S
Brandt
Jason
J
Albert
Marilyn
M
Blacker
Deborah
D
Hyman
Bradley
B
Stern
Yaakov
Y
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D010054:Brief Psychiatric Rating Scale; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology
D016229:Amyloid beta-Peptides