Journal ArticleDOI
Phases of Aβ-deposition in the human brain and its relevance for the development of AD
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TLDR
Aβ-deposition in the entire brain follows a distinct sequence in which the regions are hierarchically involved and expands anterogradely into regions that receive neuronal projections from regions already exhibiting Aβ.Abstract:
Background: The deposition of the amyloid β protein (Aβ) is a histopathologic hallmark of AD. The regions of the medial temporal lobe (MTL) are hierarchically involved in Aβ-deposition. Objective: To clarify whether there is a hierarchical involvement of the regions of the entire brain as well and whether there are differences in the expansion of Aβ-pathology between clinically proven AD cases and nondemented cases with AD-related pathology, the authors investigated 47 brains from demented and nondemented patients with AD-related pathology covering all phases of β-amyloidosis in the MTL (AβMTL phases) and four control brains without any AD-related pathology. Methods: Aβ deposits were detected by the use of the Campbell-Switzer silver technique and by immunohistochemistry in sections covering all brain regions and brainstem nuclei. It was analyzed how often distinct regions exhibited Aβ deposits. Results: In the first of five phases in the evolution of β-amyloidosis Aβ deposits are found exclusively in the neocortex. The second phase is characterized by the additional involvement of allocortical brain regions. In phase 3, diencephalic nuclei, the striatum, and the cholinergic nuclei of the basal forebrain exhibit Aβ deposits as well. Several brainstem nuclei become additionally involved in phase 4. Phase 5, finally, is characterized by cerebellar Aβ-deposition. The 17 clinically proven AD cases exhibit Aβ-phases 3, 4, or 5. The nine nondemented cases with AD-related Aβ pathology show Aβ-phases 1, 2, or 3. Conclusions: Aβ-deposition in the entire brain follows a distinct sequence in which the regions are hierarchically involved. Aβ-deposition, thereby, expands anterogradely into regions that receive neuronal projections from regions already exhibiting Aβ. There are also indications that clinically proven AD cases with full-blown β-amyloidosis may be preceded in early stages by nondemented cases exhibiting AD-related Aβ pathology.read more
Citations
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Journal ArticleDOI
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B.
William E. Klunk,Henry Engler,Agneta Nordberg,Yanming Wang,G. Blomqvist,Daniel P. Holt,Mats Bergström,Irina Savitcheva,Guo Feng Huang,Sergio Estrada,Birgitta Ausén,Manik L. Debnath,Julien Barletta,Julie C. Price,Johan Sandell,Brian J. Lopresti,Anders Wall,Pernilla Koivisto,Gunnar Antoni,Chester A. Mathis,Bengt Långström +20 more
TL;DR: The results suggest that PET imaging with the novel tracer, PIB, can provide quantitative information on amyloid deposits in living subjects.
Journal ArticleDOI
Neuropathological Alterations in Alzheimer Disease
TL;DR: Postmortem studies have enabled the staging of the progression of both amyloid and tangle pathologies, and the development of diagnostic criteria that are now used worldwide, and these cross-sectional neuropathological data have been largely validated by longitudinal in vivo studies using modern imaging biomarkers such as amyloids PET and volumetric MRI.
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National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease
Bradley T. Hyman,Creighton H. Phelps,Thomas G. Beach,Eileen H. Bigio,Nigel J. Cairns,Maria C. Carrillo,Dennis W. Dickson,Charles Duyckaerts,Matthew P. Frosch,Eliezer Masliah,Suzanne S. Mirra,Peter T. Nelson,Julie A. Schneider,Dietmar Rudolf Thal,Bill Thies,John Q. Trojanowski,Harry V. Vinters,Thomas J. Montine +17 more
TL;DR: The new guidelines recognize the pre‐clinical stage of AD, enhance the assessment of AD to include amyloid accumulation as well as neurofibrillary change and neuritic plaques, and establish protocols for the neuropathologic assessment of Lewy body disease, vascular brain injury, hippocampal sclerosis, and TDP‐43 inclusions.
Journal ArticleDOI
National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach
Thomas J. Montine,Creighton H. Phelps,Thomas G. Beach,Eileen H. Bigio,Nigel J. Cairns,Dennis W. Dickson,Charles Duyckaerts,Matthew P. Frosch,Eliezer Masliah,Suzanne S. Mirra,Peter T. Nelson,Julie A. Schneider,Dietmar Rudolf Thal,John Q. Trojanowski,Harry V. Vinters,Bradley T. Hyman +15 more
TL;DR: A practical guide for the implementation of recently revised National Institute on Aging–Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer’s disease is presented.
Journal ArticleDOI
Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature
Peter T. Nelson,Irina Alafuzoff,Eileen H. Bigio,Constantin Bouras,Heiko Braak,Nigel J. Cairns,Rudolph J. Castellani,Barbara J. Crain,Peter Davies,Kelly Del Tredici,Charles Duyckaerts,Matthew P. Frosch,Vahram Haroutunian,Patrick R. Hof,Christine M. Hulette,Bradley T. Hyman,Takeshi Iwatsubo,Kurt A. Jellinger,Gregory A. Jicha,Eniko Veronika Kovari,Walter A. Kukull,James B. Leverenz,Seth Love,Seth Love,Ian R. A. Mackenzie,David M. A. Mann,Eliezer Masliah,Ann C. McKee,Thomas J. Montine,John C. Morris,Julie A. Schneider,Joshua A. Sonnen,Dietmar Rudolf Thal,John Q. Trojanowski,Juan C. Troncoso,Thomas Wisniewski,Randall L. Woltjer,Thomas G. Beach +37 more
TL;DR: Evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of A&bgr; plaques and neurofibrillary tangles.
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