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Vol. 62, No. 2, 2009
Issue release date: July 2009
Eur Neurol 2009;62:93–98

Large Vessel Cerebral Atherosclerosis Is Not in Direct Association with Neuropathological Lesions of Alzheimer’s Disease

Luoto T.M. · Haikonen S. · Haapasalo H. · Goebeler S. · Huhtala H. · Erkinjuntti T. · Karhunen P.J.
aDepartment of Forensic Medicine, University of Tampere, bDepartment of Pathology, Tampere University Hospital, cSchool of Public Health, University of Tampere, Tampere, and dDepartment of Neurology, Helsinki University Central Hospital, Helsinki, Finland

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Introduction: Cerebral hypoperfusion caused by large vessel atherosclerosis has been suggested to be associated with the pathogenesis of sporadic Alzheimer’s disease (AD). Atherosclerosis and AD share risk factors such as age, diabetes, hypercholesterolemia, hypertension and apolipoprotein E ε4 (APOE ε4) allele. We studied the association between atherosclerosis of the circle of Willis (CW) and AD neuropathology in a large autopsy sample. Methods: The present study comprised a consecutive autopsy series (n = 466) representing noninstitutionalized general population aged 50 years and over (mean 70.8, SD 11.5 years). The atherosclerosis of CW was scored semiquantitatively and the amyloid plaque (AP) load in the frontal cortex and the number of neurofibrillary tangles (NFT) in the hippocampus were measured. Results: In a linear regression model, AP percentage area was associated with age (p < 0.0001) and APOE ε4 allele (p < 0.0001), but not with CW score (p = 0.70) or gender (p = 0.11). Similarly, the NFT count was predicted only by age (p > 0.0001), and not by CW score (p = 0.36), gender (p = 0.41) or APOE ε4 allele (p = 0.072). Conclusion: Our results suggest that cerebral large vessel atherosclerosis is not in direct association with APs or NFTs – hallmarks of AD neuropathology.

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  1. Parker GR, Cathcart HM, Huang R, Lanham IS, Corder EH, Poduslo SE: Apolipoprotein gene E4 allele promoter polymorphisms as risk factors for Alzheimer’s disease. Psychiatr Genet 2005;15:271–275.
  2. Corder EH, Ghebremedhin E, Taylor MG, Thal DR, Ohm TG, Braak H: The biphasic relationship between regional brain senile plaque and neurofibrillary tangle distributions: modification by age, sex, and APOE polymorphism. Ann N Y Acad Sci 2004;1019:24–28.
  3. Polvikoski T, Sulkava R, Myllykangas L, Notkola IL, Niinistö L, Verkkoniemi A, Kainulainen K, Kontula K, Pérez-Tur J, Hardy J, Haltia M: Prevalence of Alzheimer’s disease in very elderly people: a prospective neuropathological study. Neurology 2001;56:1690–1696.
  4. Kivipelto M, Ngandu T, Laatikainen T, Winblad B, Soininen H, Tuomilehto J: Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol 2006;5:735–741.
  5. Snowdon DA: Aging and Alzheimer’s disease: lessons from the nun study. Gerontologist 1997;37:150–156.
  6. Kalback W, Esh C, Castaño EM, Rahman A, Kokjohn T, Luehrs DC, Sue L, Cisneros R, Gerber F, Richardson C, Bohrmann B, Walker DG, Beach TG, Roher AE: Atherosclerosis, vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer’s disease. Neurol Res 2004;26:525–539.
  7. Beach TG, Wilson JR, Sue LI, Newell A, Poston M, Cisneros R, Pandya Y, Esh C, Connor DJ, Sabbagh M, Walker DG, Roher AE: Circle of Willis atherosclerosis: association with Alzheimer’s disease, neuritic plaques and neurofibrillary tangles. Acta Neuropathologica (Berlin) 2007;113:13–21.
  8. Roher AE, Esh C, Kokjohn TA, Kalback W, Luehrs DC, Seward JD, Sue LI, Beach TG: Circle of Willis atherosclerosis is a risk factor for sporadic Alzheimer’s disease. Arterioscler Thromb Vasc Biol 2003;23:2055–2062.
  9. Roher AE, Esh C, Rahman A, Kokjohn TA, Beach TG: Atherosclerosis of cerebral arteries in Alzheimer disease. Stroke 2004;35:2623–2627.
  10. Roher AE, Kokjohn TA, Beach TG: An association with great implications: vascular pathology and Alzheimer disease. Alzheimer Dis Assoc Disord 2006;20:73–75.
  11. de la Torre JC: Is Alzheimer’s disease preceded by neurodegeneration or cerebral hypoperfusion? Ann Neurol 2005;57:783–784.
  12. de la Torre JC: Is Alzheimer’s disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. Lancet Neurol 2004;3:184–190.
  13. Iadecola C, Gorelick PB: Converging pathogenic mechanisms in vascular and neurodegenerative dementia. Stroke 2003;34:335–337.
  14. Iadecola C: Atherosclerosis and neurodegeneration: unexpected conspirators in Alzheimer’s dementia. Arterioscler Thromb Vasc Biol 2003;23:1951–1953.
  15. Honig LS, Kukull W, Mayeux R: Atherosclerosis and AD: analysis of data from the US National Alzheimer’s Coordinating Center. Neurology 2005;64:494–500.
  16. Ruitenberg A, den Heijer T, Bakker SL, van Swieten JC, Koudstaal PJ, Hofman A, Breteler MM: Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol 2005;57:789–794.
  17. Aho L, Jolkkonen J, Alafuzoff I: Beta-amyloid aggregation in human brains with cerebrovascular lesions. Stroke 2006;37:2940–2945.
  18. Alafuzoff I, Helisalmi S, Mannermaa A, Soininen H: Severity of cardiovascular disease, apolipoprotein E genotype, and brain pathology in aging and dementia. Ann N Y Acad Sci 2000;903:244–251.
  19. Alafuzoff I, Helisalmi S, Mannermaa A, Riekkinen P, Soininen H: Beta-amyloid load is not influenced by the severity of cardiovascular disease in aged and demented patients. Stroke 1999;30:613–618.
  20. 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.
  21. Khachaturian ZS: Diagnosis of Alzheimer’s disease. Arch Neurol 1985;42:1097–1105.
  22. Braak H, Braak E: Staging of Alzheimer’s disease-related neurofibrillary changes. Neurobiol Aging 1995;16:271–278; discussion 278–284.
  23. Harding AJ, Kril JJ, Halliday GM: Practical measures to simplify the Braak tangle staging method for routine pathological screening. Acta Neuropathol (Berlin) 2000;99:199–208.
  24. Hixson JE, Vernier DT: Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 1990;31:545–548.

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