Traumatic brain injury as a risk factor for Alzheimer disease. Comparison of two retrospective autopsy cohorts with evaluation of ApoE genotype.

Kurt A Jellinger,W Paulus,C Wrocklage,I Litvan

doi:10.1186/1471-2377-1-3

Kurt A Jellinger, W Paulus + Show 2 more

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https://doi.org/10.1186/1471-2377-1-3

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Journal: BMC Neurology	Publication Date: Jul 30, 2001
Citations: 101	License type: cc-by

Affiliation: University of Münster, Jackson Foundation

Abstract

Background and PurposeThe 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.Material and MethodsWe 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.Results1. TBE series: 12.1 % showed definite and 10.3% probable AD (mean age 77.6 and 75.2 years), only 2/13 with ApoEε3/4. From 45 (77.6%) non-AD cases (mean age 78.2 years), 3 had ApoEε3/4. 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 ApoEε4 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 ApoEε4 allele. TBI incidence was slightly lower than 8.5% in the clinical MIRAGE study.ConclusionsThe results of this first retrospective autopsy study of TBI, ApoEε allele frequency, and AD confirm clinical studies suggesting severe TBI to be a risk factor for the development AD higher in subjects lacking ApoEε4 alleles. Further studies in larger autopsy series are needed to elucidate the relationship between TBI, genetic predisposition, and AD.

Highlights

While some genetic risk factors, e.g. apolipoprotein (ApoE)ε4, predispose the elderly to develop Alzheimer disease (AD), the role of traumatic brain injury (TBI) in the pathogenesis of AD is still controversial
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
It is well established that deposition of amyloid β peptide (Aβ) known to play an important role in the pathogenesis of AD, in fatal TBI is associated with an ApoEε4 allele [10,11] and that TBI may induce tau pathology with the formation of neurofibrillary tangles, another major histological marker of AD [12,13], the mechanisms by which TBI may induce the formation of AD pathology are still unknown, and several interpretations have been proposed [13,14]

Summary

Introduction

While some genetic risk factors, e.g. apolipoprotein (ApoE)ε4, predispose the elderly to develop Alzheimer disease (AD), the role of traumatic brain injury (TBI) in the pathogenesis of AD is still controversial. Among longitudinal studies [6,7,8,9], two reported a significantly increased riks of developing AD in subjects with previous history of TBI [8,9] A recent study of 1776 US World War II navy veterans showed that moderate and severe TBI in early adulthood, rated by the duration of loss of consciousness or posttraumatic amnesia, was associated with increased risk of AD and dementia in late life (assessed by clinical protocols).

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