Beta-amyloid burden is not associated with rates of brain atrophy.
OBJECTIVE
To test the hypothesis that beta-amyloid (Abeta) burden is associated with rates of brain atrophy.


METHODS
Forty-five subjects who had been prospectively studied, died, and had an autopsy diagnosis of low, intermediate, or high probability of Alzheimer's disease who had two volumetric head magnetic resonance imaging scans were identified. Compact and total (compact + diffuse) Abeta burden was measured using a computerized image analyzer with software program to detect the proportion of gray matter occupied by Abeta. Visual ratings of Abeta burden were also performed. The boundary shift integral was used to calculate change over time in whole-brain and ventricular volume. All boundary shift integral results were annualized by adjusting for scan interval. Demographics, cognitive measures, clinical diagnoses, apolipoprotein E genotype, neurofibrillary tangle (NFT) pathology, and vascular lesion burden were determined.


RESULTS
There was no correlation between compact or total Abeta burden, or visual Abeta ratings, and rates of brain loss or ventricular expansion in all subjects. However, significant correlations were observed between rates of brain loss and age, Braak NFT stage, and change over time in cognitive measures. These features also correlated with rates of ventricular expansion. The rates of brain loss and ventricular expansion were greater in demented compared with nondemented subjects.


CONCLUSIONS
These findings suggest that rate of brain volume loss is not determined by the amount of insoluble Abeta in the gray matter.
Josephs
Keith A
KA
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA. josephs.keith@mayo.edu
Whitwell
Jennifer L
JL
Ahmed
Zeshan
Z
Shiung
Maria M
MM
Weigand
Stephen D
SD
Knopman
David S
DS
Boeve
Bradley F
BF
Parisi
Joseph E
JE
Petersen
Ronald C
RC
Dickson
Dennis W
DW
Jack
Clifford R
CR
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics; D001284:Atrophy / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D001344:Autopsy; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D020547:Lateral Ventricles / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012720:Severity of Illness Index; D013997:Time Factors
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E