Effects of closed traumatic brain injury and genetic factors on the development of Alzheimer's disease.
In order to assess the impact of traumatic brain injury (TBI) and Apolipoprotein E (ApoE) allele frequency on the development of Alzheimer's disease (AD), we examined: (i) the incidence of AD pathology in 55 consecutive autopsy cases (mean age +/- SD 77.6 +/- 7.3 years) with residual closed TBI lesions and (ii) the frequency of TBI residuals in 53 age-matched autopsy proven AD cases. In both series, ApoE was evaluated from archival paraffin-embedded brain material. The results were as follows: (i) In the TBI series, 12.7% showed Consortium to Establish a Registry for Alzheimer's disease (CERAD) definite and 9.1% probable AD, only one with ApoEepsilon4. From the remaining 43 non-AD cases, three had ApoEepsilon4. The prevalence of 21.8% AD in this small autopsy cohort was significantly higher than 3.3% in a recent large clinical series and 14% in the general population over the age of 70. (ii) In the AD cohort with ApoEepsilon4 allele frequency of 30% similar to other AD series, residuals of TBI were seen in 4 brains (7.5%), all lacking the ApoEepsilon4 allele. TBI incidence was slightly higher than 8.5% in the clinical MIRAGE study. The results of this first retrospective autopsy study of TBI, ApoE allele frequency, and AD confirms clinical studies suggesting severe TBI to be a risk factor for the development of AD particularly in subjects lacking ApoEepsilon4.
Jellinger
K A
KA
L. Boltzmann Institute of Clinical Neurobiology, Vienna, Austria, Institute of Neuropathology, University of Münster School of Medicine, Münster, Germany. kurt.jellinger@univie.ac.at
Paulus
W
W
Wrocklage
C
C
Litvan
I
I
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D001930:Brain Injuries / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E