Skip to main content Skip to main navigation menu Skip to site footer

Brain pathological changes from population-based studies

  • Yuan Cao
  • Mei-Ying Huang
  • Mei-Jun Shu
  • Yi-Cheng Zhu


Brain structural and cerebrovascular changes and neurodegenerative pathologies are common and inadequately elucidated health problems in aging brains. Prospective population-based neuropathological studies play a unique role in neuropathological research. Brain weight decrease, arteriopathy, venular collagenosis, capillary loss, and accumulation of abnormal proteins are significant pathologies in the aging process. However, studies based on true population samples are scarce, and there is an ambiguity regarding the pathogenic proteinopathy between normal aging and neurodegenerative disease. Therefore, together population-based pathological studies offer an insight into the brain changes and diseases in the aging process, which could bring progress in the research for mechanisms and therapeutic interventions. Here, we reviewed findings from truly population-based pathological studies of brain aging and a range of neurodegenerative markers to better characterize brain pathological changes.



  1. Amador-Ortiz, C., Lin, W. L., Ahmed, Z., Personett, D., Davies, P., Duara, R., . . . Dickson, D. W. (2007). TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease. Ann Neurol, 61(5), 435-445.
  2. Arenaza-Urquijo, E. M., & Vemuri, P. (2018). Resistance vs resilience to Alzheimer disease: Clarifying terminology for preclinical studies. Neurology, 90(15), 695-703.
  3. Arnold, S. J., Dugger, B. N., & Beach, T. G. (2013). TDP-43 deposition in prospectively followed, cognitively normal elderly individuals: correlation with argyrophilic grains but not other concomitant pathologies. Acta Neuropathol, 126(1), 51-57.
  4. Arvanitakis, Z., Capuano, A. W., Leurgans, S. E., Buchman, A. S., Bennett, D. A., & Schneider, J. A. (2017). The Relationship of Cerebral Vessel Pathology to Brain Microinfarcts. Brain Pathol, 27(1), 77-85.
  5. Bell, M. A., & Ball, M. J. (1981). Morphometric comparison of hippocampal microvasculature in ageing and demented people: diameters and densities. Acta Neuropathol, 53(4), 299-318.
  6. Ben-Shlomo, Y., & Wenning, G. (1994). Incidental Lewy body disease. Lancet, 344(8935), 1503.
  7. Bennett, D. A., Schneider, J. A., Arvanitakis, Z., Kelly, J. F., Aggarwal, N. T., Shah, R. C., & Wilson, R. S. (2006). Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology, 66(12), 1837-1844.
  8. Bennett, D. A., Schneider, J. A., Buchman, A. S., Barnes, L. L., Boyle, P. A., & Wilson, R. S. (2012). Overview and findings from the rush Memory and Aging Project. Curr Alzheimer Res, 9(6), 646-663.
  9. Bennett, D. A., Schneider, J. A., Buchman, A. S., Mendes de Leon, C., Bienias, J. L., & Wilson, R. S. (2005). The Rush Memory and Aging Project: study design and baseline characteristics of the study cohort. Neuroepidemiology, 25(4), 163-175.
  10. Bloch, A., Probst, A., Bissig, H., Adams, H., & Tolnay, M. (2006). Alpha-synuclein pathology of the spinal and peripheral autonomic nervous system in neurologically unimpaired elderly subjects. Neuropathol Appl Neurobiol, 32(3), 284-295.
  11. Braak, H., & Braak, E. (1987). Argyrophilic grains: characteristic pathology of cerebral cortex in cases of adult onset dementia without Alzheimer changes. Neurosci Lett, 76(1), 124-127.
  12. Braak, H., & Braak, E. (1998). Argyrophilic grain disease: frequency of occurrence in different age categories and neuropathological diagnostic criteria. J Neural Transm (Vienna), 105(8-9), 801-819.
  13. Brayne, C., McCracken, C., & Matthews, F. E. (2006). Cohort profile: the Medical Research Council Cognitive Function and Ageing Study (CFAS). Int J Epidemiol, 35(5), 1140-1145.
  14. Brayne, C., Richardson, K., Matthews, F. E., Fleming, J., Hunter, S., Xuereb, J. H., . . . Cambridge City Over-75s Cohort Cc75c Study Neuropathology, C. (2009). Neuropathological correlates of dementia in over-80-year-old brain donors from the population-based Cambridge city over-75s cohort (CC75C) study. J Alzheimers Dis, 18(3), 645-658.
  15. Brenowitz, W. D., Keene, C. D., Hawes, S. E., Hubbard, R. A., Longstreth, W. T., Jr., Woltjer, R. L., . . . Kukull, W. A. (2017). Alzheimer's disease neuropathologic change, Lewy body disease, and vascular brain injury in clinic- and community-based samples. Neurobiol Aging, 53, 83-92.
  16. Brown, W. R., & Thore, C. R. (2011). Review: cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol Appl Neurobiol, 37(1), 56-74.
  17. Buchman, A. S., Nag, S., Leurgans, S. E., Miller, J., VanderHorst, V., Bennett, D. A., & Schneider, J. A. (2018). Spinal Lewy body pathology in older adults without an antemortem diagnosis of Parkinson's disease. Brain Pathol, 28(4), 560-568.
  18. Buratti, E., & Baralle, F. E. (2012). TDP-43: gumming up neurons through protein-protein and protein-RNA interactions. Trends Biochem Sci, 37(6), 237-247.
  19. Chung, E. J., Babulal, G. M., Monsell, S. E., Cairns, N. J., Roe, C. M., & Morris, J. C. (2015). Clinical Features of Alzheimer Disease With and Without Lewy Bodies. JAMA Neurol, 72(7), 789-796.
  20. Cykowski, M. D., Takei, H., Van Eldik, L. J., Schmitt, F. A., Jicha, G. A., Powell, S. Z., & Nelson, P. T. (2016). Hippocampal Sclerosis but Not Normal Aging or Alzheimer Disease Is Associated With TDP-43 Pathology in the Basal Forebrain of Aged Persons. J Neuropathol Exp Neurol, 75(5), 397-407.
  21. Dekaban, A. S. (1978). Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights. Ann Neurol, 4(4), 345-356.
  22. Ding, Z. T., Wang, Y., Jiang, Y. P., Yoshida, M., Mimuro, M., Inagaki, T., . . . Hashizume, Y. (2006). Argyrophilic grain disease: frequency and neuropathology in centenarians. Acta Neuropathol, 111(4), 320-328.
  23. Dugger, B. N., & Dickson, D. W. (2017). Pathology of Neurodegenerative Diseases. Cold Spring Harb Perspect Biol, 9(7).
  24. Fleming, J., Zhao, E., O'Connor, D. W., Pollitt, P. A., & Brayne, C. (2007). Cohort profile: the Cambridge City over-75s Cohort (CC75C). Int J Epidemiol, 36(1), 40-46.
  25. Foltynie, T., Matthews, F. E., Ishihara, L., & Brayne, C. (2006). The frequency and validity of self-reported diagnosis of Parkinson's Disease in the UK elderly: MRC CFAS cohort. BMC Neurol, 6, 29.
  26. Fujishiro, H., Uchikado, H., Arai, T., Hasegawa, M., Akiyama, H., Yokota, O., . . . Hirayasu, Y. (2009). Accumulation of phosphorylated TDP-43 in brains of patients with argyrophilic grain disease. Acta Neuropathol, 117(2), 151-158.
  27. Ganz, A. B., Beker, N., Hulsman, M., Sikkes, S., Netherlands Brain, B., Scheltens, P., . . . Holstege, H. (2018). Neuropathology and cognitive performance in self-reported cognitively healthy centenarians. Acta Neuropathol Commun, 6(1), 64.
  28. Grau-Rivera, O., Gelpi, E., Rey, M. J., Valldeoriola, F., Tolosa, E., Compta, Y., & Martí, M. J. (2013). Prominent psychiatric symptoms in patients with Parkinson's disease and concomitant argyrophilic grain disease. J Neurol, 260(12), 3002-3009.
  29. Grinberg, L. T., Wang, X., Wang, C., Sohn, P. D., Theofilas, P., Sidhu, M., . . . Seeley, W. W. (2013). Argyrophilic grain disease differs from other tauopathies by lacking tau acetylation. Acta Neuropathol, 125(4), 581-593.
  30. Hamilton, R. L. (2000). Lewy bodies in Alzheimer's disease: a neuropathological review of 145 cases using alpha-synuclein immunohistochemistry. Brain Pathol, 10(3), 378-384.
  31. Hartmann, P., Ramseier, A., Gudat, F., Mihatsch, M. J., & Polasek, W. (1994). [Normal weight of the brain in adults in relation to age, sex, body height and weight]. Pathologe, 15(3), 165-170. (Das Normgewicht des Gehirns beim Erwachsenen in Abhängigkeit von Alter, Geschlecht, Körpergrösse und Gewicht.)
  32. Hassler, O. (1967). Arterial deformities in senile brains. The occurrence of the deformities in a large autopsy series and some aspects of their functional significance. Acta Neuropathol, 8(3), 219-229.
  33. Henry-Feugeas, M. C. (2008). Alzheimer's disease in late-life dementia: a minor toxic consequence of devastating cerebrovascular dysfunction. Med Hypotheses, 70(4), 866-875.
  34. Homma, T., Mochizuki, Y., Takahashi, K., & Komori, T. (2015). Medial temporal regional argyrophilic grain as a possible important factor affecting dementia in Parkinson's disease. Neuropathology, 35(5), 441-451.
  35. Hou, Y., Dan, X., Babbar, M., Wei, Y., Hasselbalch, S. G., Croteau, D. L., & Bohr, V. A. (2019). Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol, 15(10), 565-581.
  36. Hyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., . . . Montine, T. J. (2012). National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement, 8(1), 1-13.
  37. Ikeda, C., Yokota, O., Nagao, S., Ishizu, H., Oshima, E., Hasegawa, M., . . . Yamada, N. (2016). The Relationship Between Development of Neuronal and Astrocytic Tau Pathologies in Subcortical Nuclei and Progression of Argyrophilic Grain Disease. Brain Pathol, 26(4), 488-505.
  38. Incidence of dementia and cognitive decline in over-75s in Cambridge overview of cohort study. (1998).
  39. Jellinger, K. A. (2003). Neuropathological spectrum of synucleinopathies. Mov Disord, 18 Suppl 6, S2-12.
  40. Jellinger, K. A. (2004). Lewy body-related alpha-synucleinopathy in the aged human brain. J Neural Transm (Vienna), 111(10-11), 1219-1235.
  41. Josephs, K. A., Whitwell, J. L., Parisi, J. E., Knopman, D. S., Boeve, B. F., Geda, Y. E., . . . Dickson, D. W. (2008). Argyrophilic grains: a distinct disease or an additive pathology? Neurobiol Aging, 29(4), 566-573.
  42. Keage, H. A., Carare, R. O., Friedland, R. P., Ince, P. G., Love, S., Nicoll, J. A., . . . Brayne, C. (2009). Population studies of sporadic cerebral amyloid angiopathy and dementia: a systematic review. BMC Neurol, 9, 3.
  43. Keage, H. A., Hunter, S., Matthews, F. E., Ince, P. G., Hodges, J., Hokkanen, S. R., . . . Brayne, C. (2014). TDP-43 pathology in the population: prevalence and associations with dementia and age. J Alzheimers Dis, 42(2), 641-650.
  44. Klos, K. J., Ahlskog, J. E., Josephs, K. A., Apaydin, H., Parisi, J. E., Boeve, B. F., . . . Dickson, D. W. (2006). Alpha-synuclein pathology in the spinal cords of neurologically asymptomatic aged individuals. Neurology, 66(7), 1100-1102.
  45. Knopman, D. S., Parisi, J. E., Salviati, A., Floriach-Robert, M., Boeve, B. F., Ivnik, R. J., . . . Petersen, R. C. (2003). Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol, 62(11), 1087-1095.
  46. Koga, S., Kouri, N., Walton, R. L., Ebbert, M. T. W., Josephs, K. A., Litvan, I., . . . Dickson, D. W. (2018). Corticobasal degeneration with TDP-43 pathology presenting with progressive supranuclear palsy syndrome: a distinct clinicopathologic subtype. Acta Neuropathol, 136(3), 389-404.
  47. Kovacs, G. G., Ferrer, I., Grinberg, L. T., Alafuzoff, I., Attems, J., Budka, H., . . . Dickson, D. W. (2016). Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy. Acta Neuropathol, 131(1), 87-102.
  48. Kritsilis, M., S, V. R., Koutsoudaki, P. N., Evangelou, K., Gorgoulis, V. G., & Papadopoulos, D. (2018). Ageing, Cellular Senescence and Neurodegenerative Disease. Int J Mol Sci, 19(10).
  49. Latimer, C. S., Burke, B. T., Liachko, N. F., Currey, H. N., Kilgore, M. D., Gibbons, L. E., . . . Keene, C. D. (2019). Resistance and resilience to Alzheimer's disease pathology are associated with reduced cortical pTau and absence of limbic-predominant age-related TDP-43 encephalopathy in a community-based cohort. Acta Neuropathol Commun, 7(1), 91.
  50. Liao, Y. Z., Ma, J., & Dou, J. Z. (2022). The Role of TDP-43 in Neurodegenerative Disease. Mol Neurobiol, 59(7), 4223-4241.
  51. Markesbery, W. R., Jicha, G. A., Liu, H., & Schmitt, F. A. (2009). Lewy body pathology in normal elderly subjects. J Neuropathol Exp Neurol, 68(7), 816-822.
  52. Martinez-Lage, P., & Munoz, D. G. (1997). Prevalence and disease associations of argyrophilic grains of Braak. J Neuropathol Exp Neurol, 56(2), 157-164.
  53. Masliah, E., Hansen, L. A., Quijada, S., DeTeresa, R., Alford, M., Kauss, J., & Terry, R. (1991). Late onset dementia with argyrophilic grains and subcortical tangles or atypical progressive supranuclear palsy? Ann Neurol, 29(4), 389-396.
  54. Matthews, F. E., Arthur, A., Barnes, L. E., Bond, J., Jagger, C., Robinson, L., & Brayne, C. (2013). A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II. Lancet, 382(9902), 1405-1412.
  55. Mattila, P., Togo, T., & Dickson, D. W. (2002). The subthalamic nucleus has neurofibrillary tangles in argyrophilic grain disease and advanced Alzheimer's disease. Neurosci Lett, 320(1-2), 81-85.
  56. Mikolaenko, I., Pletnikova, O., Kawas, C. H., O'Brien, R., Resnick, S. M., Crain, B., & Troncoso, J. C. (2005). Alpha-synuclein lesions in normal aging, Parkinson disease, and Alzheimer disease: evidence from the Baltimore Longitudinal Study of Aging (BLSA). J Neuropathol Exp Neurol, 64(2), 156-162.
  57. Montine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., . . . Hyman, B. T. (2012). National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol, 123(1), 1-11.
  58. Nag, S., Yu, L., Wilson, R. S., Chen, E. Y., Bennett, D. A., & Schneider, J. A. (2017). TDP-43 pathology and memory impairment in elders without pathologic diagnoses of AD or FTLD. Neurology, 88(7), 653-660.
  59. Nakashima-Yasuda, H., Uryu, K., Robinson, J., Xie, S. X., Hurtig, H., Duda, J. E., . . . Trojanowski, J. Q. (2007). Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases. Acta Neuropathol, 114(3), 221-229.
  60. Nascimento, C., Suemoto, C. K., Rodriguez, R. D., Alho, A. T., Leite, R. P., Farfel, J. M., . . . Grinberg, L. T. (2016). Higher Prevalence of TDP-43 Proteinopathy in Cognitively Normal Asians: A Clinicopathological Study on a Multiethnic Sample. Brain Pathol, 26(2), 177-185.
  61. Nelson, P. T., Gal, Z., Wang, W. X., Niedowicz, D. M., Artiushin, S. C., Wycoff, S., . . . Fardo, D. W. (2019). TDP-43 proteinopathy in aging: Associations with risk-associated gene variants and with brain parenchymal thyroid hormone levels. Neurobiol Dis, 125, 67-76.
  62. Nelson, P. T., Trojanowski, J. Q., Abner, E. L., Al-Janabi, O. M., Jicha, G. A., Schmitt, F. A., . . . Ighodaro, E. T. (2016). "New Old Pathologies": AD, PART, and Cerebral Age-Related TDP-43 With Sclerosis (CARTS). J Neuropathol Exp Neurol, 75(6), 482-498.
  63. Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., . . . Lee, V. M. (2006). Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science, 314(5796), 130-133.
  64. Ninomiya, T. (2018). Japanese Legacy Cohort Studies: The Hisayama Study. Journal of epidemiology, 28(11), 444-451.
  65. The Nun Study_ risk factors for pathology and clinical-pathologic correlations. (2012).
  66. Oinas, M., Polvikoski, T., Sulkava, R., Myllykangas, L., Juva, K., Notkola, I. L., . . . Paetau, A. (2009). Neuropathologic findings of dementia with lewy bodies (DLB) in a population-based Vantaa 85+ study. J Alzheimers Dis, 18(3), 677-689.
  67. Outeiro, T. F., Koss, D. J., Erskine, D., Walker, L., Kurzawa-Akanbi, M., Burn, D., . . . McKeith, I. (2019). Dementia with Lewy bodies: an update and outlook. Mol Neurodegener, 14(1), 5.
  68. Overview and Findings from the Religious Orders Study. (2012).
  69. Overview and Findings from the Rush Memory and Aging Project. (2013).
  70. Parkkinen, L., Soininen, H., & Alafuzoff, I. (2003). Regional distribution of alpha-synuclein pathology in unimpaired aging and Alzheimer disease. J Neuropathol Exp Neurol, 62(4), 363-367.
  71. Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. (2001). The Lancet, 357(9251), 169-175.
  72. Peters, R. (2006). Ageing and the brain. Postgrad Med J, 82(964), 84-88.
  73. Riley, K. P., Snowdon, D. A., & Markesbery, W. R. (2002). Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study. Ann Neurol, 51(5), 567-577.
  74. Robinson, A. C., Davidson, Y. S., Horan, M. A., Pendleton, N., & Mann, D. M. A. (2018). Pathological Correlates of Cognitive Impairment in The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age. J Alzheimers Dis, 64(2), 483-496.
  75. Robinson, J. L., Lee, E. B., Xie, S. X., Rennert, L., Suh, E., Bredenberg, C., . . . Trojanowski, J. Q. (2018). Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated. Brain, 141(7), 2181-2193.
  76. Rodriguez, R. D., Suemoto, C. K., Molina, M., Nascimento, C. F., Leite, R. E., de Lucena Ferretti-Rebustini, R. E., . . . Grinberg, L. T. (2016). Argyrophilic Grain Disease: Demographics, Clinical, and Neuropathological Features From a Large Autopsy Study. J Neuropathol Exp Neurol, 75(7), 628-635.
  77. Roher, A. E., Kuo, Y. M., Esh, C., Knebel, C., Weiss, N., Kalback, W., . . . Kokjohn, T. A. (2003). Cortical and leptomeningeal cerebrovascular amyloid and white matter pathology in Alzheimer's disease. Mol Med, 9(3-4), 112-122.
  78. Sabbagh, M. N., Sandhu, S. S., Farlow, M. R., Vedders, L., Shill, H. A., Caviness, J. N., . . . Beach, T. G. (2009). Correlation of clinical features with argyrophilic grains at autopsy. Alzheimer Dis Assoc Disord, 23(3), 229-233.
  79. Saito, Y., Nakahara, K., Yamanouchi, H., & Murayama, S. (2002). Severe involvement of ambient gyrus in dementia with grains. J Neuropathol Exp Neurol, 61(9), 789-796.
  80. Saito, Y., Ruberu, N. N., Sawabe, M., Arai, T., Tanaka, N., Kakuta, Y., . . . Murayama, S. (2004). Staging of argyrophilic grains: an age-associated tauopathy. J Neuropathol Exp Neurol, 63(9), 911-918.
  81. SantaCruz, K. S., Sonnen, J. A., Pezhouh, M. K., Desrosiers, M. F., Nelson, P. T., & Tyas, S. L. (2011). Alzheimer disease pathology in subjects without dementia in 2 studies of aging: the Nun Study and the Adult Changes in Thought Study. J Neuropathol Exp Neurol, 70(10), 832-840.
  82. Santpere, G., & Ferrer, I. (2009). Delineation of early changes in cases with progressive supranuclear palsy-like pathology. Astrocytes in striatum are primary targets of tau phosphorylation and GFAP oxidation. Brain Pathol, 19(2), 177-187.
  83. Schneider, J. A., Aggarwal, N. T., Barnes, L., Boyle, P., & Bennett, D. A. (2009). The neuropathology of older persons with and without dementia from community versus clinic cohorts. J Alzheimers Dis, 18(3), 691-701.
  84. Schneider, J. A., Arvanitakis, Z., Yu, L., Boyle, P. A., Leurgans, S. E., & Bennett, D. A. (2012). Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies. Brain, 135(Pt 10), 3005-3014.
  85. Schwab, C., Arai, T., Hasegawa, M., Yu, S., & McGeer, P. L. (2008). Colocalization of transactivation-responsive DNA-binding protein 43 and huntingtin in inclusions of Huntington disease. J Neuropathol Exp Neurol, 67(12), 1159-1165.
  86. Sonnen, J. A., Larson, E. B., Crane, P. K., Haneuse, S., Li, G., Schellenberg, G. D., . . . Montine, T. J. (2007). Pathological correlates of dementia in a longitudinal, population-based sample of aging. Ann Neurol, 62(4), 406-413.
  87. Spillantini, M. G., Schmidt, M. L., Lee, V. M., Trojanowski, J. Q., Jakes, R., & Goedert, M. (1997). Alpha-synuclein in Lewy bodies. Nature, 388(6645), 839-840.
  88. Stern, Y., Jacobs, D., Goldman, J., Gomez-Tortosa, E., Hyman, B. T., Liu, Y., . . . Albert, M. (2001). An investigation of clinical correlates of Lewy bodies in autopsy-proven Alzheimer disease. Arch Neurol, 58(3), 460-465.
  89. Suemoto, C. K., Grinberg, L. T., Leite, R. E. P., Ferretti-Rebustini, R. E. L., Jacob-Filho, W., Yaffe, K., . . . Pasqualucci, C. A. (2018). Morphometric measurements of extracranial and intracranial atherosclerotic disease: A population-based autopsy study. Atherosclerosis, 270, 218-223.
  90. Sumikura, H., Takao, M., Hatsuta, H., Ito, S., Nakano, Y., Uchino, A., . . . Murayama, S. (2015). Distribution of α-synuclein in the spinal cord and dorsal root ganglia in an autopsy cohort of elderly persons. Acta Neuropathol Commun, 3, 57.
  91. Takao, M., Hirose, N., Arai, Y., Mihara, B., & Mimura, M. (2016). Neuropathology of supercentenarians - four autopsy case studies. Acta Neuropathol Commun, 4(1), 97.
  92. Tanprasertsuk, J., Johnson, E. J., Johnson, M. A., Poon, L. W., Nelson, P. T., Davey, A., . . . Scott, T. M. (2019). Clinico-Neuropathological Findings in the Oldest Old from the Georgia Centenarian Study. J Alzheimers Dis, 70(1), 35-49.
  93. Tatsumi, S., Mimuro, M., Iwasaki, Y., Takahashi, R., Kakita, A., Takahashi, H., & Yoshida, M. (2014). Argyrophilic grains are reliable disease-specific features of corticobasal degeneration. J Neuropathol Exp Neurol, 73(1), 30-38.
  94. Thal, D. R., Schultz, C., Botez, G., Del Tredici, K., Mrak, R. E., Griffin, W. S., . . . Ghebremedhin, E. (2005). The impact of argyrophilic grain disease on the development of dementia and its relationship to concurrent Alzheimer's disease-related pathology. Neuropathol Appl Neurobiol, 31(3), 270-279.
  95. Togo, T., Sahara, N., Yen, S. H., Cookson, N., Ishizawa, T., Hutton, M., . . . Dickson, D. W. (2002). Argyrophilic grain disease is a sporadic 4-repeat tauopathy. J Neuropathol Exp Neurol, 61(6), 547-556.
  96. Tolnay, M., Spillantini, M. G., Goedert, M., Ulrich, J., Langui, D., & Probst, A. (1997). Argyrophilic grain disease: widespread hyperphosphorylation of tau protein in limbic neurons. Acta Neuropathol, 93(5), 477-484.
  97. Tschanz, J. T., Treiber, K., Norton, M. C., Welsh-Bohmer, K. A., Toone, L., Zandi, P. P., . . . Breitner, J. C. (2005). A population study of Alzheimer's disease: findings from the Cache County Study on Memory, Health, and Aging. Care Manag J, 6(2), 107-114.
  98. Uchino, A., Takao, M., Hatsuta, H., Sumikura, H., Nakano, Y., Nogami, A., . . . Murayama, S. (2015). Incidence and extent of TDP-43 accumulation in aging human brain. Acta Neuropathol Commun, 3, 35.
  99. Uryu, K., Nakashima-Yasuda, H., Forman, M. S., Kwong, L. K., Clark, C. M., Grossman, M., . . . Neumann, M. (2008). Concomitant TAR-DNA-binding protein 43 pathology is present in Alzheimer disease and corticobasal degeneration but not in other tauopathies. J Neuropathol Exp Neurol, 67(6), 555-564.
  100. Wakisaka, Y., Furuta, A., Tanizaki, Y., Kiyohara, Y., Iida, M., & Iwaki, T. (2003). Age-associated prevalence and risk factors of Lewy body pathology in a general population: the Hisayama study. Acta Neuropathol, 106(4), 374-382.
  101. Weller, R. O., Massey, A., Newman, T. A., Hutchings, M., Kuo, Y. M., & Roher, A. E. (1998). Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer's disease. Am J Pathol, 153(3), 725-733.
  102. Wennberg, A. M., Whitwell, J. L., Tosakulwong, N., Weigand, S. D., Murray, M. E., Machulda, M. M., . . . Josephs, K. A. (2019). The influence of tau, amyloid, alpha-synuclein, TDP-43, and vascular pathology in clinically normal elderly individuals. Neurobiol Aging, 77, 26-36.
  103. White, L., Petrovitch, H., Hardman, J., Nelson, J., Davis, D. G., Ross, G. W., . . . Markesbery, W. R. (2002). Cerebrovascular pathology and dementia in autopsied Honolulu-Asia Aging Study participants. Ann N Y Acad Sci, 977, 9-23.
  104. Wilson, A. C., Dugger, B. N., Dickson, D. W., & Wang, D. S. (2011). TDP-43 in aging and Alzheimer's disease - a review. Int J Clin Exp Pathol, 4(2), 147-155.
  105. Wilson, R. S., Yu, L., Trojanowski, J. Q., Chen, E. Y., Boyle, P. A., Bennett, D. A., & Schneider, J. A. (2013). TDP-43 pathology, cognitive decline, and dementia in old age. JAMA Neurol, 70(11), 1418-1424.
  106. Xu, Y. F., Gendron, T. F., Zhang, Y. J., Lin, W. L., D'Alton, S., Sheng, H., . . . Petrucelli, L. (2010). Wild-type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice. J Neurosci, 30(32), 10851-10859.
  107. Yokota, O., Davidson, Y., Bigio, E. H., Ishizu, H., Terada, S., Arai, T., . . . Mann, D. M. (2010). Phosphorylated TDP-43 pathology and hippocampal sclerosis in progressive supranuclear palsy. Acta Neuropathol, 120(1), 55-66.
  108. Yokota, O., Miki, T., Ikeda, C., Nagao, S., Takenoshita, S., Ishizu, H., . . . Yamada, N. (2018). Neuropathological comorbidity associated with argyrophilic grain disease. Neuropathology, 38(1), 82-97.
  109. Zaccai, J., Ince, P., & Brayne, C. (2006). Population-based neuropathological studies of dementia: design, methods and areas of investigation--a systematic review. BMC Neurol, 6, 2.
  110. Zaccai, J., Ince, P., & Brayne, C. (2006). Population-based neuropathological studies of dementia: design, methods and areas of investigation--a systematic review. BMC neurology, 6, 2-2.

How to Cite

Cao, Yuan, et al. “Brain Pathological Changes from Population-Based Studies”. Human Brain, vol. 1, no. 1, Nov. 2022, pp. 63-76, doi:10.37819/hb.001.001.0205 .


83 1



Article Details

Most Read This Month


Copyright (c) 2022 Yuan Cao, Mei-Ying Huang, Mei-Jun Shu, Yi-Cheng Zhu

Creative Commons License

This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License.