Apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begins in middle age - PubMed (original) (raw)
Comparative Study
doi: 10.1002/ana.21696.
Affiliations
- PMID: 19557866
- DOI: 10.1002/ana.21696
Comparative Study
Apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begins in middle age
Eloise Kok et al. Ann Neurol. 2009 Jun.
Abstract
Objective: To study the prevalence and age dependency of senile plaques (SP) and neurofibrillary tangles (NFT), the brain changes characteristic of Alzheimer disease (AD), and their association with apolipoprotein E (APOE) genotypes in a community-dwelling normal population.
Methods: This neuropathological study used both silver staining and A beta immunohistochemistry in brain tissue microarrays, including SP coverage and NFT counts from frontal cortex and hippocampus, and APOE genotyping, and was performed on a consecutive prospective series of 603 subjects (aged between 0 and 97 years) of an unselected population living outside of institutions. Cases were subjected to autopsy following sudden or unexpected out-of-hospital death, covering 22.1% of the mortality of Tampere, Finland and its surroundings. None died of AD, although 22 (3.7%) were demented and 10 (1.7%) had memory problems.
Results: Of the series, 30.8% had SP, and 42.1% had NFT; these occurred more commonly among females and showed a strong relationship with age. Both changes had already appeared at around 30 years of age, reaching an occurrence of almost 100% in the oldest. SP were more frequent in APOE epsilon 4-carriers compared with noncarriers in every age group except the oldest (>90 years). The difference was most evident during the ages 50 to 59 years, where 40.7% of epsilon 4-carriers had SP, compared with 8.2% in noncarriers (odds ratio, 8.39; 95% confidence interval, 2.55-27.62). The difference in NFT prevalence between APOE genotypes was not statistically significant in any age group.
Interpretation: The brain changes associated with AD may already begin developing early in middle age, especially among APOE epsilon 4 carriers.
Comment in
- Alzheimer disease: multiple causes, multiple effects of apolipoprotein E4, and multiple therapeutic approaches.
Mahley RW, Huang Y. Mahley RW, et al. Ann Neurol. 2009 Jun;65(6):623-5. doi: 10.1002/ana.21736. Ann Neurol. 2009. PMID: 19557874 No abstract available.
Similar articles
- APOE, vascular pathology, and the AD brain.
Yip AG, McKee AC, Green RC, Wells J, Young H, Cupples LA, Farrer LA. Yip AG, et al. Neurology. 2005 Jul 26;65(2):259-65. doi: 10.1212/01.wnl.0000168863.49053.4d. Neurology. 2005. PMID: 16043796 - Large vessel cerebral atherosclerosis is not in direct association with neuropathological lesions of Alzheimer's disease.
Luoto TM, Haikonen S, Haapasalo H, Goebeler S, Huhtala H, Erkinjuntti T, Karhunen PJ. Luoto TM, et al. Eur Neurol. 2009;62(2):93-8. doi: 10.1159/000222779. Epub 2009 Jun 12. Eur Neurol. 2009. PMID: 19521084 - Apolipoprotein E interaction with the neurofibrillary tangles and senile plaques in Alzheimer disease: implications for disease pathogenesis.
Richey PL, Siedlak SL, Smith MA, Perry G. Richey PL, et al. Biochem Biophys Res Commun. 1995 Mar 17;208(2):657-63. doi: 10.1006/bbrc.1995.1389. Biochem Biophys Res Commun. 1995. PMID: 7695621 - Morphological substrates of cognitive decline in nonagenarians and centenarians: a new paradigm?
Imhof A, Kövari E, von Gunten A, Gold G, Rivara CB, Herrmann FR, Hof PR, Bouras C, Giannakopoulos P. Imhof A, et al. J Neurol Sci. 2007 Jun 15;257(1-2):72-9. doi: 10.1016/j.jns.2007.01.025. Epub 2007 Feb 15. J Neurol Sci. 2007. PMID: 17303173 Review. - Cerebral amyloid angiopathy and its relationship to Alzheimer's disease.
Thal DR, Griffin WS, de Vos RA, Ghebremedhin E. Thal DR, et al. Acta Neuropathol. 2008 Jun;115(6):599-609. doi: 10.1007/s00401-008-0366-2. Epub 2008 Mar 28. Acta Neuropathol. 2008. PMID: 18369648 Review.
Cited by
- Prevalence of arrhythmia-associated gene mutations and risk of sudden cardiac death in the Finnish population.
Lahtinen AM, Havulinna AS, Noseworthy PA, Jula A, Karhunen PJ, Perola M, Newton-Cheh C, Salomaa V, Kontula K. Lahtinen AM, et al. Ann Med. 2013 Jun;45(4):328-35. doi: 10.3109/07853890.2013.783995. Epub 2013 May 8. Ann Med. 2013. PMID: 23651034 Free PMC article. - Existing Pittsburgh Compound-B positron emission tomography thresholds are too high: statistical and pathological evaluation.
Villeneuve S, Rabinovici GD, Cohn-Sheehy BI, Madison C, Ayakta N, Ghosh PM, La Joie R, Arthur-Bentil SK, Vogel JW, Marks SM, Lehmann M, Rosen HJ, Reed B, Olichney J, Boxer AL, Miller BL, Borys E, Jin LW, Huang EJ, Grinberg LT, DeCarli C, Seeley WW, Jagust W. Villeneuve S, et al. Brain. 2015 Jul;138(Pt 7):2020-33. doi: 10.1093/brain/awv112. Epub 2015 May 6. Brain. 2015. PMID: 25953778 Free PMC article. - ApoE and TDP-43 neuropathology in two siblings with familial FTLD-motor neuron disease.
Vossel KA, Bien-Ly N, Bernardo A, Rascovsky K, Karydas A, Rabinovici GD, Sidhu M, Huang EJ, Miller BL, Huang Y, Seeley WW. Vossel KA, et al. Neurocase. 2013;19(3):295-301. doi: 10.1080/13554794.2012.667124. Epub 2012 Apr 18. Neurocase. 2013. PMID: 22512241 Free PMC article. - Polygenic risk of Alzheimer disease is associated with early- and late-life processes.
Mormino EC, Sperling RA, Holmes AJ, Buckner RL, De Jager PL, Smoller JW, Sabuncu MR; Alzheimer's Disease Neuroimaging Initiative. Mormino EC, et al. Neurology. 2016 Aug 2;87(5):481-8. doi: 10.1212/WNL.0000000000002922. Epub 2016 Jul 6. Neurology. 2016. PMID: 27385740 Free PMC article. - Apolipoprotein E as a Therapeutic Target in Alzheimer's Disease: A Review of Basic Research and Clinical Evidence.
Yamazaki Y, Painter MM, Bu G, Kanekiyo T. Yamazaki Y, et al. CNS Drugs. 2016 Sep;30(9):773-89. doi: 10.1007/s40263-016-0361-4. CNS Drugs. 2016. PMID: 27328687 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous