α1-CHYMOTRYPSIN AND α1-TRYPSIN IMMUNOLOCALIZE WITH NEUROFIBRILLARY TANGLES AND SENILE PLAQUES OF ALZHEIMER DISEASE

Abstract Context.—Down syndrome patients who live to middle age invariably develop the neuropathologic features of Alzheimer disease, providing a unique situation in which to study the early and sequential development of these changes. Objective.—To study the development of amyloid deposits, senile plaques, astrocytic and microglial reactions, and neurofibrillary tangles in the brains of young individuals (<30 years of age) with Down syndrome. Methods.—Histologic and immunocytochemical study of a series of autopsy brains (n = 14, from subjects aged 11 months to 56 years, with 9 subjects <30 years) examined at the Office of the Chief Medical Examiner of the State of Maryland and The Johns Hopkins Hospital. Results.—The principal observations included the presence of intraneuronal Aβ immunostaining in the hippocampus and cerebral cortex of very young Down syndrome patients (preceding the extracellular deposition of Aβ) and the formation of senile plaques and neurofibrillary tangles. Conclusions.—We propose the following sequence of events in the development of neuropathologic changes of Alzheimer disease in Down syndrome: (1) intracellular accumulation of Aβ in neurons and astrocytes, (2) deposition of extracellular Aβ and formation of diffuse plaques, and (3) development of neuritic plaques and neurofibrillary tangles with activation of microglial cells.

Download Full-text

Inducible Nitric Oxide Synthase Immunoreactivity in the Alzheimer Disease Hippocampus: Association with Hirano Bodies, Neurofibrillary Tangles, and Senile Plaques

Journal of Neuropathology & Experimental Neurology ◽

10.1097/00005072-199911000-00006 ◽

1999 ◽

Vol 58 (11) ◽

pp. 1163-1169 ◽

Cited By ~ 73

Author(s):

Sunhee C. Lee ◽

Meng-Liang Zhao ◽

Asao Hirano ◽

Dennis W. Dickson

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Alzheimer Disease ◽

Inducible Nitric Oxide Synthase ◽

Neurofibrillary Tangles ◽

Senile Plaques ◽

Hirano Bodies ◽

Oxide Synthase ◽

Inducible Nitric Oxide

Download Full-text

Apolipoprotein E Interaction with the Neurofibrillary Tangles and Senile Plaques in Alzheimer Disease: Implications for Disease Pathogenesis

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1995.1389 ◽

1995 ◽

Vol 208 (2) ◽

pp. 657-663 ◽

Cited By ~ 39

Author(s):

P.L. Richey ◽

S.L. Siedlak ◽

M.A. Smith ◽

G. Perry

Keyword(s):

Alzheimer Disease ◽

Apolipoprotein E ◽

Neurofibrillary Tangles ◽

Senile Plaques ◽

Disease Pathogenesis

Download Full-text

Structural and Chemical Studies of Pathological Fibers in Human Neurofibrillary Degeneration

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010012031x ◽

1985 ◽

Vol 43 ◽

pp. 726-729

Author(s):

K.S. Kosik ◽

L.K. Duffy ◽

S. Bakalis ◽

C. Abraham ◽

D.J. Selkoe

Keyword(s):

Monoclonal Antibodies ◽

Alzheimer Disease ◽

Human Brain ◽

Neurofibrillary Tangles ◽

Morphological Analysis ◽

High Specificity ◽

Cytoskeletal Proteins ◽

Neuritic Plaque ◽

Protein Chemistry ◽

Chemical Studies

The major structural lesions of the human brain during aging and in Alzheimer disease (AD) are the neurofibrillary tangles (NFT) and the senile (neuritic) plaque. Although these fibrous alterations have been recognized by light microscopists for almost a century, detailed biochemical and morphological analysis of the lesions has been undertaken only recently. Because the intraneuronal deposits in the NFT and the plaque neurites and the extraneuronal amyloid cores of the plaques have a filamentous ultrastructure, the neuronal cytoskeleton has played a prominent role in most pathogenetic hypotheses.The approach of our laboratory toward elucidating the origin of plaques and tangles in AD has been two-fold: the use of analytical protein chemistry to purify and then characterize the pathological fibers comprising the tangles and plaques, and the use of certain monoclonal antibodies to neuronal cytoskeletal proteins that, despite high specificity, cross-react with NFT and thus implicate epitopes of these proteins as constituents of the tangles.

Download Full-text

Faculty Opinions recommendation of Proteomic analysis of neurofibrillary tangles in Alzheimer disease identifies GAPDH as a detergent-insoluble paired helical filament tau binding protein.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1023996.297903 ◽

2005 ◽

Author(s):

George Perry

Keyword(s):

Alzheimer Disease ◽

Neurofibrillary Tangles ◽

Proteomic Analysis ◽

Binding Protein ◽

Paired Helical Filament

Download Full-text

NLRP3 Inflammasome: A Starring Role in Amyloid-β- and Tau-Driven Pathological Events in Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-210268 ◽

2021 ◽

pp. 1-22

Author(s):

Mariana Van Zeller ◽

Diogo M. Dias ◽

Ana M. Sebastião ◽

Cláudia A. Valente

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Glial Cells ◽

Neurofibrillary Tangles ◽

Nlrp3 Inflammasome ◽

Neuronal Death ◽

Inflammatory Responses ◽

Senile Plaques ◽

Amyloid Β ◽

Wide Range

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease commonly diagnosed among the elderly population. AD is characterized by the loss of synaptic connections, neuronal death, and progressive cognitive impairment, attributed to the extracellular accumulation of senile plaques, composed by insoluble aggregates of amyloid-β (Aβ) peptides, and to the intraneuronal formation of neurofibrillary tangles shaped by hyperphosphorylated filaments of the microtubule-associated protein tau. However, evidence showed that chronic inflammatory responses, with long-lasting exacerbated release of proinflammatory cytokines by reactive glial cells, contribute to the pathophysiology of the disease. NLRP3 inflammasome (NLRP3), a cytosolic multiprotein complex sensor of a wide range of stimuli, was implicated in multiple neurological diseases, including AD. Herein, we review the most recent findings regarding the involvement of NLRP3 in the pathogenesis of AD. We address the mechanisms of NLRP3 priming and activation in glial cells by Aβ species and the potential role of neurofibrillary tangles and extracellular vesicles in disease progression. Neuronal death by NLRP3-mediated pyroptosis, driven by the interneuronal tau propagation, is also discussed. We present considerable evidence to claim that NLRP3 inhibition, is undoubtfully a potential therapeutic strategy for AD.

Download Full-text