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Diffuse Amyloid-β Plaques, Neurofibrillary Tangles, and the Impact of APOE in Elderly Persons' Brains Lacking Neuritic Amyloid Plaques.
J Alzheimers Dis 2018; 64(4):1307-1324JA

Abstract

Data from a large autopsy series were analyzed to address questions pertinent to primary age-related tauopathy (PART) and Alzheimer's disease (AD): what factors are associated with increased severity of neurofibrillary degeneration in brains that lack neuritic amyloid plaques?; is there an association between Apolipoprotein E (APOE) alleles and PART pathologic severity independent of amyloid-β (Aβ) deposits?; and, how do the stains used to detect plaques and tangles impact the experimental results? Neuropathologic data were evaluated from elderly research volunteers whose brain autopsies were performed at University of Kentucky Alzheimer's Disease Center (UK-ADC; N = 145 subjects). All of the included subjects' brains lacked neuritic amyloid plaques according to the CERAD diagnostic criteria and the average final MMSE score before death was 26.8±4.6 stdev. The study incorporated evaluation of tissue with both silver histochemical stains and immunohistochemical stains to compare results; the immunohistochemical stains (Aβ and phospho-tau) were scanned and quantified using digital pathologic methods. Immunohistochemical stains provided important advantages over histochemical stains due to sensitivity and detectability via digital methods. When AD-type pathology was in its presumed earliest phases, neocortical parenchymal Aβ deposits were associated with increased medial temporal lobe neurofibrillary tangles. The observation supports the NIA-AA consensus recommendation for neuropathologic diagnoses, because even these "diffuse" Aβ deposits signal that AD pathobiologic mechanisms are occurring. Further, the data were most compatible with the hypothesis that the APOEɛ4 allele exerts its effect(s) via driving Aβ deposition, i.e., an "upstream" influence, rather than being associated directly with Aβ- independent PART pathology.

Authors+Show Affiliations

Department of Epidemiology, University of Kentucky, Lexington, KY, USA. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.Department of Pathology, Division of Neuropathology, University of Kentucky, Lexington, KY, USA.Department of Neurology, University of Kentucky, Lexington, KY, USA. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.Department of Physiology, University of Kentucky, Lexington, KY, USA. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.Department of Neuroscience, University of Kentucky, Lexington, KY, USA. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.Department of Pathology, Division of Neuropathology, University of Kentucky, Lexington, KY, USA. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

30040735

Citation

Abner, Erin L., et al. "Diffuse Amyloid-β Plaques, Neurofibrillary Tangles, and the Impact of APOE in Elderly Persons' Brains Lacking Neuritic Amyloid Plaques." Journal of Alzheimer's Disease : JAD, vol. 64, no. 4, 2018, pp. 1307-1324.
Abner EL, Neltner JH, Jicha GA, et al. Diffuse Amyloid-β Plaques, Neurofibrillary Tangles, and the Impact of APOE in Elderly Persons' Brains Lacking Neuritic Amyloid Plaques. J Alzheimers Dis. 2018;64(4):1307-1324.
Abner, E. L., Neltner, J. H., Jicha, G. A., Patel, E., Anderson, S. L., Wilcock, D. M., ... Nelson, P. T. (2018). Diffuse Amyloid-β Plaques, Neurofibrillary Tangles, and the Impact of APOE in Elderly Persons' Brains Lacking Neuritic Amyloid Plaques. Journal of Alzheimer's Disease : JAD, 64(4), pp. 1307-1324. doi:10.3233/JAD-180514.
Abner EL, et al. Diffuse Amyloid-β Plaques, Neurofibrillary Tangles, and the Impact of APOE in Elderly Persons' Brains Lacking Neuritic Amyloid Plaques. J Alzheimers Dis. 2018;64(4):1307-1324. PubMed PMID: 30040735.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diffuse Amyloid-β Plaques, Neurofibrillary Tangles, and the Impact of APOE in Elderly Persons' Brains Lacking Neuritic Amyloid Plaques. AU - Abner,Erin L, AU - Neltner,Janna H, AU - Jicha,Gregory A, AU - Patel,Ela, AU - Anderson,Sonya L, AU - Wilcock,Donna M, AU - Van Eldik,Linda J, AU - Nelson,Peter T, PY - 2018/7/25/pubmed PY - 2018/7/25/medline PY - 2018/7/25/entrez KW - Aging KW - Genie KW - MAPT KW - SNAP KW - ScanScope KW - amyloid-β KW - hippocampus KW - neuropathology KW - oldest-old SP - 1307 EP - 1324 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 64 IS - 4 N2 - Data from a large autopsy series were analyzed to address questions pertinent to primary age-related tauopathy (PART) and Alzheimer's disease (AD): what factors are associated with increased severity of neurofibrillary degeneration in brains that lack neuritic amyloid plaques?; is there an association between Apolipoprotein E (APOE) alleles and PART pathologic severity independent of amyloid-β (Aβ) deposits?; and, how do the stains used to detect plaques and tangles impact the experimental results? Neuropathologic data were evaluated from elderly research volunteers whose brain autopsies were performed at University of Kentucky Alzheimer's Disease Center (UK-ADC; N = 145 subjects). All of the included subjects' brains lacked neuritic amyloid plaques according to the CERAD diagnostic criteria and the average final MMSE score before death was 26.8±4.6 stdev. The study incorporated evaluation of tissue with both silver histochemical stains and immunohistochemical stains to compare results; the immunohistochemical stains (Aβ and phospho-tau) were scanned and quantified using digital pathologic methods. Immunohistochemical stains provided important advantages over histochemical stains due to sensitivity and detectability via digital methods. When AD-type pathology was in its presumed earliest phases, neocortical parenchymal Aβ deposits were associated with increased medial temporal lobe neurofibrillary tangles. The observation supports the NIA-AA consensus recommendation for neuropathologic diagnoses, because even these "diffuse" Aβ deposits signal that AD pathobiologic mechanisms are occurring. Further, the data were most compatible with the hypothesis that the APOEɛ4 allele exerts its effect(s) via driving Aβ deposition, i.e., an "upstream" influence, rather than being associated directly with Aβ- independent PART pathology. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/30040735/Diffuse_Amyloid_β_Plaques_Neurofibrillary_Tangles_and_the_Impact_of_APOE_in_Elderly_Persons'_Brains_Lacking_Neuritic_Amyloid_Plaques_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-180514 DB - PRIME DP - Unbound Medicine ER -