Paired helical filament tau (PHFtau) in Niemann-Pick type C disease is similar to PHFtau in Alzheimer's disease

Auer, Iwona; Schmidt, Maria Luiza Gava; Lee, V. M. Y.; Curry, Bernadette; Suzuki, Kinuko; Shin, Ryong-Woon; Pentchev, P. G.; Carstea, Eugene D.; Trojanowski, John Q.

doi:10.1007/bf00318566

Cited by 179 publications

(83 citation statements)

References 19 publications

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“…The neurodegenerative disease Niemann-Pick type C is characterized by the buildup of lipoprotein-derived cholesterol in lysosomes due to mutations in the NPC1 protein (Loftus et al 1997). Interestingly, the excessive lysosomal storage of cholesterol may in fact promote abnormal protein processing as evidenced by the appearance of PHF-tau in Niemann-Pick disease resembling that found in AD (Auer et al 1995). This is consistent with reports suggesting that altered tau processing and early PHF formation involve lysosomes of AD brains and model systems (Ikeda et al 1998(Ikeda et al , 2000Oyama et al 1998;Bendiske et al 2002).…”

Section: Alzheimer-type Protein Depositionsupporting

confidence: 87%

The neuropathogenic contributions of lysosomal dysfunction

Bahr

Bendiske

2002

Journal of Neurochemistry

177

126

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Multiple lines of evidence implicate lysosomes in a variety of pathogenic events that produce neurodegeneration. Genetic mutations that cause specific enzyme deficiencies account for more than 40 lysosomal storage disorders. These mostly pre-adult diseases are associated with abnormal brain development and mental retardation. Such disorders are characterized by intracellular deposition and protein aggregation, events also found in age-related neurodegenerative diseases including (i) Alzheimer's disease and related tauopathies (ii) Lewy body disorders and synucleinopathies such as Parkinson's disease, and (iii) Huntington's disease and other polyglutamine expansion disorders. Of particular interest for this review is evidence that alterations to the lysosomal system contribute to protein deposits associated with different types of age-related neurodegeneration. Lysosomes are in fact highly susceptible to free radical oxidative stress in the aging brain, leading to the gradual loss of their processing capacity over the lifespan of an individual. Several studies point to this lysosomal disturbance as being involved in amyloidogenic processing, formation of paired helical filaments, and the aggregation of a-synuclein and mutant huntingtin proteins. Most notably, experimentally induced lysosomal dysfunction, both in vitro and in vivo, recapitulates important pathological features of age-related diseases including the link between protein deposition and synaptic loss.

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Section: Alzheimer-type Protein Depositionsupporting

confidence: 87%

The neuropathogenic contributions of lysosomal dysfunction

Bahr

Bendiske

2002

Journal of Neurochemistry

177

126

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“…2 A striking feature of NPC pathology is the presence in brain of neurofibrillary tangles that, by an array of measures, are indistinguishable from those found in Alzheimer's disease. [3][4][5][6][7] Tangles in the latter case are thought to arise from excessive activation of a set of kinases, including glycogen synthase kinase (GSK-3␤), resulting in the hyperphosphorylation of the microtubule crosslinking protein tau and its assembly into helical filaments. Several in vitro and in vivo studies have implicated GSK-3␤ in tangle formation; 8 -10 moreover, recent work indicates that the kinase co-localizes with intraneuronal tangles and probably accumulates in neurons before the onset of pathology.…”

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confidence: 99%

Deregulation of the Phosphatidylinositol-3 Kinase Signaling Cascade Is Associated with Neurodegeneration in Npc1−/− Mouse Brain

Liu

Yao

et al. 2005

The American Journal of Pathology

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“…The latter have greatly facilitated investigation of tau hyperphosphorylation in diseases other than AD. It thus has been shown that lesions made of hyperphosphorylated tau similar to those found in AD are present in Down syndrome (11), Niemann-Pick disease type C (12)(13)(14), Gerstmann-Sträussler-Scheinker (GSS) disease with tangles (15,16), prion protein amyloid angiopathy (17), parkinsonism-dementia complex of Guam (18,19), and familial presenile dementia with tangles (20,21).…”

mentioning

confidence: 99%

Familial multiple system tauopathy with presenile dementia: A disease with abundant neuronal and glial tau filaments

Spillantini¹,

Goedert

Crowther

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

324

214

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Neurofibrillary lesions made of hyperphosphorylated microtubule-associated protein tau constitute not only one of the defining neuropathological features of Alzheimer disease but also are present in a number of other neurodegenerative diseases with dementia. Here we describe a novel autosomal dominant disease named familial ''multiple system tauopathy with presenile dementia,'' which is characterized by abundant fibrillary deposits of tau protein in both neurons and glial cells. There are no detectable deposits of ␤-amyloid. The tau deposits are in the form of twisted filaments that differ in diameter and periodicity from the paired helical filaments of Alzheimer disease. They are stained by both phosphorylation-independent and -dependent anti-tau antibodies. Moreover, tau immunoreactivity coexists with heparan sulfate in affected nerve and glial cells. Tau protein extracted from filaments of familial multiple system tauopathy with presenile dementia shows a minor 72-kDa band and two major bands of 64 and 68 kDa that contain mainly hyperphosphorylated four-repeat tau isoforms of 383 and 412 amino acids.

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Paired helical filament tau (PHFtau) in Niemann-Pick type C disease is similar to PHFtau in Alzheimer's disease

Cited by 179 publications

References 19 publications

The neuropathogenic contributions of lysosomal dysfunction

The neuropathogenic contributions of lysosomal dysfunction

Deregulation of the Phosphatidylinositol-3 Kinase Signaling Cascade Is Associated with Neurodegeneration in Npc1−/− Mouse Brain

Familial multiple system tauopathy with presenile dementia: A disease with abundant neuronal and glial tau filaments

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