Traumatic brain injury as a risk factor for Alzheimer disease. Comparison of two retrospective autopsy cohorts with evaluation of ApoE genotype.
OBJECTIVE
The impact of traumatic brain injury (TBI) on the pathogenesis of Alzheimer disease (AD) is still controversial. The aim of our retrospective autopsy study was to assess the impact of TBE and ApoE allele frequency on the development of AD.


METHODS
We examined 1. the incidence of AD pathology (Braak stageing, CERAD, NIA-Reagan Institute criteria) in 58 consecutive patients (mean age +/- SD 77.0 +/- 6.8 years) with residual closed TBI lesions, and 2. the frequency of TBI residuals in 57 age-matched autopsy proven AD cases. In both series, ApoE was evaluated from archival paraffin-embedded brain material.


RESULTS
1. TBE series: 12.1 % showed definite and 10.3% probable AD (mean age 77.6 and 75.2 years), only 2/13 with ApoEepsilon3/4. From 45 (77.6%) non-AD cases (mean age 78.2 years), 3 had ApoEepsilon3/4. The prevalence of 22.4% 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 age 70. 2. In the AD cohort with ApoEepsilon4 allele frequency of 30% similar to other AD series, residuals of closed TBI were seen in 4 brains (7%) (mean age +/- SD 78.2 +/- 6.4), all lacking the ApoEepsilon4 allele. TBI incidence was slightly lower than 8.5% in the clinical MIRAGE study.


CONCLUSIONS
The results of this first retrospective autopsy study of TBI, ApoEepsilon allele frequency, and AD confirm clinical studies suggesting severe TBI to be a risk factor for the development AD higher in subjects lacking ApoEepsilon4 alleles. Further studies in larger autopsy series are needed to elucidate the relationship between TBI, genetic predisposition, and AD.
Jellinger
K A
KA
L Boltzmann Institute of Clinical Neurobiology, Baumgartner Hoehe 1, B-Bldg, A-1140 Vienna, Austria. 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*; D001317:Austria / Q000453:epidemiology; D001930:Brain Injuries / Q000453:epidemiology* / Q000473:pathology; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E