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
TLDR
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.Abstract:
Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. β-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective for understanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of Aβ plaques and neurofibrillary tangles. Although Aβ plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.read more
Citations
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Journal ArticleDOI
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies.
Justin M. Long,David M. Holtzman +1 more
TL;DR: Recent advances in the understanding of AD pathobiology are reviewed and current treatment strategies are discussed, highlighting recent clinical trials and opportunities for developing future disease-modifying therapies.
Journal ArticleDOI
Inflammation as a central mechanism in Alzheimer's disease
Jefferson W. Kinney,Shane M. Bemiller,Andrew S. Murtishaw,Amanda M. Leisgang,Arnold Salazar,Bruce T. Lamb +5 more
TL;DR: An overview of inflammation in AD is provided and a detailed coverage of a number of microglia‐related signaling mechanisms that have been implicated in AD are reviewed.
Journal ArticleDOI
Primary age-related tauopathy (PART): a common pathology associated with human aging
John F. Crary,John Q. Trojanowski,Julie A. Schneider,Jose F. Abisambra,Erin L. Abner,Irina Alafuzoff,Steven E. Arnold,Johannes Attems,Thomas G. Beach,Eileen H. Bigio,Nigel J. Cairns,Dennis W. Dickson,Marla Gearing,Lea T. Grinberg,Lea T. Grinberg,Patrick R. Hof,Bradley T. Hyman,Kurt A. Jellinger,Gregory A. Jicha,Gabor G. Kovacs,David S. Knopman,Julia Kofler,Walter A. Kukull,Ian R. A. Mackenzie,Eliezer Masliah,Ann C. McKee,Thomas J. Montine,Melissa E. Murray,Janna H. Neltner,Ismael Santa-Maria,William W. Seeley,Alberto Serrano-Pozo,Michael L. Shelanski,Thor D. Stein,Masaki Takao,Dietmar Rudolf Thal,Jonathan B. Toledo,Juan C. Troncoso,Jean Paul G. Vonsattel,Charles L. White,Thomas Wisniewski,Randall L. Woltjer,Masahito Yamada,Peter T. Nelson +43 more
TL;DR: A new term is recommended, “primary age-related tauopathy” (PART), to describe a pathology that is commonly observed in the brains of aged individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time.
Journal ArticleDOI
Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors
Stephen S. Dominy,Casey C. Lynch,Florian Ermini,Malgorzata Benedyk,Agata Marczyk,Andrei Konradi,Mai Nguyen,Ursula Haditsch,Debasish Raha,Christina Griffin,Leslie J. Holsinger,Shirin Arastu-Kapur,Samer Kaba,Alexander Lee,Mark I. Ryder,Barbara Potempa,Piotr Mydel,Piotr Mydel,Annelie Hellvard,Annelie Hellvard,Karina Adamowicz,Hatice Hasturk,Hatice Hasturk,Glenn D Walker,Eric C. Reynolds,Richard L.M. Faull,Maurice A. Curtis,Mike Dragunow,Jan Potempa,Jan Potempa +29 more
TL;DR: Gingipains from Porphyromonas gingivalis drive Alzheimer’s pathology and can be blocked with small-molecule inhibitors, suggesting that gingipain inhibitors could be valuable for treating P. gedivalis brain colonization and neurodegeneration in Alzheimer's disease.
Journal ArticleDOI
PET Imaging of Tau Deposition in the Aging Human Brain
Michael Schöll,Michael Schöll,Samuel N. Lockhart,Daniel R. Schonhaut,James P. O'Neil,Mustafa Janabi,Rik Ossenkoppele,Rik Ossenkoppele,Rik Ossenkoppele,Suzanne L. Baker,Jacob W. Vogel,Jamie Faria,Henry Schwimmer,Gil D. Rabinovici,Gil D. Rabinovici,Gil D. Rabinovici,William J. Jagust,William J. Jagust +17 more
TL;DR: In this paper, the authors defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition, and found that older age was associated with increased tracers retention in regions of the medial temporal lobe, which predicted worse episodic memory performance.
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