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Published in: BMC Neurology 1/2001

Open Access 01-12-2001 | Research article

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

Authors: Kurt A Jellinger, Werner Paulus, Christian Wrocklage, Irene Litvan

Published in: BMC Neurology | Issue 1/2001

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Abstract

Background and Purpose

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.

Material and 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 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.

Conclusions

The 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.
Literature
1.
go back to reference Lye TC, Shores EA: Traumatic brain injury as a risk factor for Alzheimer's disease: a review. Neuropsychol Rev. 2000, 10: 115-129. 10.1023/A:1009068804787.CrossRefPubMed Lye TC, Shores EA: Traumatic brain injury as a risk factor for Alzheimer's disease: a review. Neuropsychol Rev. 2000, 10: 115-129. 10.1023/A:1009068804787.CrossRefPubMed
3.
go back to reference Launer LJ, Andersen K, Dewey ME, Letenneur L, Ott A, Amaducci LA, Brayne C, Copeland JR, Dartigues JF, Kragh-Sorensen P, et al: Rates and risk factors for dementia and Alzheimer's disease: results from EURODEM pooled analyses. EURODEM Incidence Research Group and Work Groups. European Studies of Dementia. Neurology. 1999, 52: 78-84.CrossRefPubMed Launer LJ, Andersen K, Dewey ME, Letenneur L, Ott A, Amaducci LA, Brayne C, Copeland JR, Dartigues JF, Kragh-Sorensen P, et al: Rates and risk factors for dementia and Alzheimer's disease: results from EURODEM pooled analyses. EURODEM Incidence Research Group and Work Groups. European Studies of Dementia. Neurology. 1999, 52: 78-84.CrossRefPubMed
4.
go back to reference Mehta KM, Ott A, Kalmijn S, Slooter AJ, van Duijn CM, Hofinan A, Breteler MM: Head trauma and risk of dementia and Alzheimer's disease: The Rotterdam Study. Neurology. 1999, 53: 1959-1962.CrossRefPubMed Mehta KM, Ott A, Kalmijn S, Slooter AJ, van Duijn CM, Hofinan A, Breteler MM: Head trauma and risk of dementia and Alzheimer's disease: The Rotterdam Study. Neurology. 1999, 53: 1959-1962.CrossRefPubMed
5.
go back to reference Guo Z, Cupples LA, Kurz A, Auerbach SH, Volicer L, Chui H, Green RC, Sadovnick AD, Duara R, DeCarli C, et al: Head injury and the risk of AD in the MIRAGE study. Neurology. 2000, 54: 1316-1323.CrossRefPubMed Guo Z, Cupples LA, Kurz A, Auerbach SH, Volicer L, Chui H, Green RC, Sadovnick AD, Duara R, DeCarli C, et al: Head injury and the risk of AD in the MIRAGE study. Neurology. 2000, 54: 1316-1323.CrossRefPubMed
6.
go back to reference Katzman R, Aronson M, Fuld P, Kawas C, Brown T, Morgenstem H, Frishman W, Gidez L, Eder H, Ooi WL: Development of dementing illnesses in an 80-year-old volunteer cohort. Ann Neurol. 1989, 25: 317-324.CrossRefPubMed Katzman R, Aronson M, Fuld P, Kawas C, Brown T, Morgenstem H, Frishman W, Gidez L, Eder H, Ooi WL: Development of dementing illnesses in an 80-year-old volunteer cohort. Ann Neurol. 1989, 25: 317-324.CrossRefPubMed
7.
go back to reference Williams DB, Annegers JF, Kokmen PC, O'Brien PC, Kurland LT: Brain injury and neurologic sequelae: a cohort study of dementia, parkinsonism, and amyotrophic lateral sclerosis. Neurology. 1991, 41: 1554-1557.CrossRefPubMed Williams DB, Annegers JF, Kokmen PC, O'Brien PC, Kurland LT: Brain injury and neurologic sequelae: a cohort study of dementia, parkinsonism, and amyotrophic lateral sclerosis. Neurology. 1991, 41: 1554-1557.CrossRefPubMed
8.
go back to reference Schofield PW, Tang M, Marder K, Bell K, Dooneief G, Chun M, Sano M, Stem Y, Mayeux R: Alzheimer's disease after remote head injury: an incidence study. J Neurol Neurosurg Psychiatry. 1997, 62: 119-124.CrossRefPubMedPubMedCentral Schofield PW, Tang M, Marder K, Bell K, Dooneief G, Chun M, Sano M, Stem Y, Mayeux R: Alzheimer's disease after remote head injury: an incidence study. J Neurol Neurosurg Psychiatry. 1997, 62: 119-124.CrossRefPubMedPubMedCentral
9.
go back to reference Plassman BA, Havlik BA, Steffens BA, Helms BA, Newman BA, Drosdick BA, Phillips BA, Gau BA, Welsh-Bohmer KA, Burke JR, et al: Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias. Neurology. 2000, 55: 1158-1166.CrossRefPubMed Plassman BA, Havlik BA, Steffens BA, Helms BA, Newman BA, Drosdick BA, Phillips BA, Gau BA, Welsh-Bohmer KA, Burke JR, et al: Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias. Neurology. 2000, 55: 1158-1166.CrossRefPubMed
10.
go back to reference Nicoll JAR, Roberts GW, Graham DI: Apolipoprotein Eε4 allele is associated with deposition of amyloid β-protein following head injury. Nature Med. 1995, 1: 135-137.CrossRefPubMed Nicoll JAR, Roberts GW, Graham DI: Apolipoprotein Eε4 allele is associated with deposition of amyloid β-protein following head injury. Nature Med. 1995, 1: 135-137.CrossRefPubMed
11.
go back to reference Horsburgh K, Cole GM, Yang F, Savage BD, Greenberg BD, Gentleman SM, Graham DI, Nicoll JAR: β-Amyloid (Aβ) 42(43), Aβ 42, Aβ 40 and apo E immunostaining of plaques in fatal head injury. Neuropathol Appl Neurobiol. 2000, 26: 124-132. 10.1046/j.1365-2990.2000.026002124.x.CrossRefPubMed Horsburgh K, Cole GM, Yang F, Savage BD, Greenberg BD, Gentleman SM, Graham DI, Nicoll JAR: β-Amyloid (Aβ) 42(43), Aβ 42, Aβ 40 and apo E immunostaining of plaques in fatal head injury. Neuropathol Appl Neurobiol. 2000, 26: 124-132. 10.1046/j.1365-2990.2000.026002124.x.CrossRefPubMed
12.
go back to reference Smith C, Graham DI, Nicoll JAR: Tau immunohistochemistry in acute head injury. Neuropathol Appl Neurobiol. 2001, 27: 151- Smith C, Graham DI, Nicoll JAR: Tau immunohistochemistry in acute head injury. Neuropathol Appl Neurobiol. 2001, 27: 151-
13.
go back to reference Geddes JF, Vowles GH, Nicoll JA, Revesz T: Neuronal cytoskeletal changes are an early consequence of repetitive head injury. Acta Neuropathol. 1999, 98: 171-178. 10.1007/s004010051066.CrossRefPubMed Geddes JF, Vowles GH, Nicoll JA, Revesz T: Neuronal cytoskeletal changes are an early consequence of repetitive head injury. Acta Neuropathol. 1999, 98: 171-178. 10.1007/s004010051066.CrossRefPubMed
14.
go back to reference Graham DI, McIntosh WL, Maxwell WL, Nicoll JAR: Recent advances in neurotrauma. J Neuropathol Exp Neurol. 2000, 59: 641-651.CrossRefPubMed Graham DI, McIntosh WL, Maxwell WL, Nicoll JAR: Recent advances in neurotrauma. J Neuropathol Exp Neurol. 2000, 59: 641-651.CrossRefPubMed
16.
go back to reference Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, Van Belle G, Berg L: The Consortium to establish a registry for Alzheimer's disease (CERAD) II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991, 41: 479-486.CrossRefPubMed Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, Van Belle G, Berg L: The Consortium to establish a registry for Alzheimer's disease (CERAD) II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991, 41: 479-486.CrossRefPubMed
17.
go back to reference Braak H, Braak E: Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991, 82: 239-259.CrossRefPubMed Braak H, Braak E: Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991, 82: 239-259.CrossRefPubMed
18.
go back to reference Hyman BT, Trojanowski JQ: Editorial on Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol. 1997, 56: 1095-1097.CrossRefPubMed Hyman BT, Trojanowski JQ: Editorial on Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol. 1997, 56: 1095-1097.CrossRefPubMed
19.
go back to reference Wrocklage C, Bernatik J, Stefan H, Jellinger KA, Paulus W: Apolipoprotein E genotype in epilepsy and schizophrenia patients with cognitive deficits. Acta Neuropathol. 1999, 99: 557- Wrocklage C, Bernatik J, Stefan H, Jellinger KA, Paulus W: Apolipoprotein E genotype in epilepsy and schizophrenia patients with cognitive deficits. Acta Neuropathol. 1999, 99: 557-
20.
go back to reference McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, Salmon DP, Lowe J, Mirra SS, Byrne EJ, et al: Clinical and pathological diagnosis of dementia with Lewy bodies (DLB): report of the CDLB International Workshop. Neurology. 1996, 47: 1113-1124.CrossRefPubMed McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, Salmon DP, Lowe J, Mirra SS, Byrne EJ, et al: Clinical and pathological diagnosis of dementia with Lewy bodies (DLB): report of the CDLB International Workshop. Neurology. 1996, 47: 1113-1124.CrossRefPubMed
21.
go back to reference Harrington CR, Louwagie J, Rossau R, Vanmechelen E, Perry RH, Perry EK, Xuereb JH, Roth M, Wischik CM: Influence of apolipoprotein E genotype on senile dementia of the Alzheimer and Lewy body types. Significance for etiological theories of Alzheimer's disease. Am J Pathol. 1994, 45: 1472-1484. Harrington CR, Louwagie J, Rossau R, Vanmechelen E, Perry RH, Perry EK, Xuereb JH, Roth M, Wischik CM: Influence of apolipoprotein E genotype on senile dementia of the Alzheimer and Lewy body types. Significance for etiological theories of Alzheimer's disease. Am J Pathol. 1994, 45: 1472-1484.
22.
go back to reference Egensperger R, Bancher C, Kösel S, Jellinger K, Mehraein P, Graeber MB: The apolipoprotein Eε4 allele in Parkinson's disease with Alzheimer lesions. Biochem Biophys Res Commun. 1996, 224: 484-486. 10.1006/bbrc.1996.1053.CrossRefPubMed Egensperger R, Bancher C, Kösel S, Jellinger K, Mehraein P, Graeber MB: The apolipoprotein Eε4 allele in Parkinson's disease with Alzheimer lesions. Biochem Biophys Res Commun. 1996, 224: 484-486. 10.1006/bbrc.1996.1053.CrossRefPubMed
23.
go back to reference Bancher C, Egensperger R, Kösel S, Jellinger K, Graeber MB: Low prevalence of apolipoprotein Eε4 allele in the neurofibrillary tangle predominant form of senile dementia. Acta Neuropathol. 1997, 94: 403-409. 10.1007/s004010050726.CrossRefPubMed Bancher C, Egensperger R, Kösel S, Jellinger K, Graeber MB: Low prevalence of apolipoprotein Eε4 allele in the neurofibrillary tangle predominant form of senile dementia. Acta Neuropathol. 1997, 94: 403-409. 10.1007/s004010050726.CrossRefPubMed
24.
go back to reference Corder EH, Lannfelt L, Bogdanovic N, Fratiglioni L, Mori H: The role of apoe polymorphisms in late-onset dementias. Cell Molec Life Sci. 1998, 54: 928-934. 10.1007/s000180050223.CrossRefPubMed Corder EH, Lannfelt L, Bogdanovic N, Fratiglioni L, Mori H: The role of apoe polymorphisms in late-onset dementias. Cell Molec Life Sci. 1998, 54: 928-934. 10.1007/s000180050223.CrossRefPubMed
25.
go back to reference Rebeck GW, Peris TT, West HL, Sodhi P, Lipsitz LA, Hyman BT: Reduced apolipoprotein epsilon 4 allele frequency in the oldest old Alzheimer's patients and cognitively normal individuals. Neurology. 1994, 44: 1513-1516.CrossRefPubMed Rebeck GW, Peris TT, West HL, Sodhi P, Lipsitz LA, Hyman BT: Reduced apolipoprotein epsilon 4 allele frequency in the oldest old Alzheimer's patients and cognitively normal individuals. Neurology. 1994, 44: 1513-1516.CrossRefPubMed
26.
go back to reference Geldmacher DS, Whitehouse PJ: Evaluation of dementia. N Engl J Med. 1996, 335: 330-336. 10.1056/NEJM199608013350507.CrossRefPubMed Geldmacher DS, Whitehouse PJ: Evaluation of dementia. N Engl J Med. 1996, 335: 330-336. 10.1056/NEJM199608013350507.CrossRefPubMed
27.
go back to reference Reischies FM, Geiselmann B, Gessner R, Kanowski S, Wagner M, Wemicke F, Helmchen H: Demenz bei Hochbetagten. Ergebnisse der Berliner Altersstudie. Nervenarzt. 1997, 68: 719-729. 10.1007/s001150050186.CrossRefPubMed Reischies FM, Geiselmann B, Gessner R, Kanowski S, Wagner M, Wemicke F, Helmchen H: Demenz bei Hochbetagten. Ergebnisse der Berliner Altersstudie. Nervenarzt. 1997, 68: 719-729. 10.1007/s001150050186.CrossRefPubMed
28.
go back to reference Thomassen R, van Schaick HW, Blansjaar BA: Prevalence of dementia over age 100. Neurology. 1998, 50: 283-286.CrossRefPubMed Thomassen R, van Schaick HW, Blansjaar BA: Prevalence of dementia over age 100. Neurology. 1998, 50: 283-286.CrossRefPubMed
29.
go back to reference Bachman DL, Wolf PA, Linn R, Knoefel JE, Cobb J, Belanger A, RB D'Agostino, White LR: Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study. Neurology. 1992, 42: 115-119.CrossRefPubMed Bachman DL, Wolf PA, Linn R, Knoefel JE, Cobb J, Belanger A, RB D'Agostino, White LR: Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study. Neurology. 1992, 42: 115-119.CrossRefPubMed
30.
go back to reference Pfeffer RI, Afifi AA, Chance JM: Prevalence of Alzheimer's disease in a retirement community. Am J Epidemiol. 1987, 125: 420-436.PubMed Pfeffer RI, Afifi AA, Chance JM: Prevalence of Alzheimer's disease in a retirement community. Am J Epidemiol. 1987, 125: 420-436.PubMed
31.
go back to reference Hy LX, Keller DM: Prevalence of AD among whites. A summary by levels of severity. Neurology. 2000, 55: 198-204.CrossRefPubMed Hy LX, Keller DM: Prevalence of AD among whites. A summary by levels of severity. Neurology. 2000, 55: 198-204.CrossRefPubMed
32.
go back to reference Sabo T, Lomnitski L, Nyska A, Beni S, Maronpot RR, Shohami E, Roses AD, DM : Michaelson: Susceptibility of transgenic mice expressing human apolipoprotein E to closed head injury: the allele E3 is neuroprotective whereas E4 increases fatalities. Neuroscience. 2000, 101: 879-884. 10.1016/S0306-4522(00)00438-3.CrossRefPubMed Sabo T, Lomnitski L, Nyska A, Beni S, Maronpot RR, Shohami E, Roses AD, DM : Michaelson: Susceptibility of transgenic mice expressing human apolipoprotein E to closed head injury: the allele E3 is neuroprotective whereas E4 increases fatalities. Neuroscience. 2000, 101: 879-884. 10.1016/S0306-4522(00)00438-3.CrossRefPubMed
Metadata
Title
Traumatic brain injury as a risk factor for Alzheimer disease. Comparison of two retrospective autopsy cohorts with evaluation of ApoE genotype
Authors
Kurt A Jellinger
Werner Paulus
Christian Wrocklage
Irene Litvan
Publication date
01-12-2001
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2001
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/1471-2377-1-3

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