Coexistence of Alzheimer-type neuropathology in Creutzfeldt-Jakob disease

Hainfellner, Johannes A.; Wanschitz, Julia; Jellinger, K. A.; Liberski, P. P.; Gullotta, F.; Budka, Herbert

doi:10.1007/s004010050870

Cited by 133 publications

(119 citation statements)

References 20 publications

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“…Coexisting AD pathology has been described in CJD. In an Austrian neuropathological longitudinal study of 110 CJD patients, coexisting AD pathological changes have been described in 11% of cases of which 20% showed NFT pathology [6]. Another study reported NFT pathology in 19% of 65 sporadic CJD patients [19].…”

Section: Discussionmentioning

confidence: 99%

Dissociation between CSF total tau and tau protein phosphorylated at threonine 231 in Creutzfeldt–Jakob disease

Büerger

Otto

Teipel

et al. 2006

Neurobiology of Aging

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To study the potential diagnostic value of abnormally phosphorylated tau protein in Creutzfeldt-Jakob disease (CJD) compared to Alzheimer's disease (AD), we determined levels of tau phosphorylated at threonine 231 (p-tau 231 ) and of total tau (t-tau) in cerebrospinal fluid (CSF) of CJD patients, AD patients, and healthy controls (HC). CJD patients showed excessively high t-tau levels but relatively low p-tau 231 concentrations compared to the AD group. t-tau alone yielded the best diagnostic accuracy to differentiate between CJD and AD patients, when compared to p-tau 231 and the p-tau 231 /t-tau ratio (97, 78, and 95% correctly allocated cases, respectively). Our findings indicate a dissociation in the direction of change in CSF levels of t-tau and p-tau 231 in CJD when compared to AD.

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Section: Discussionmentioning

confidence: 99%

Dissociation between CSF total tau and tau protein phosphorylated at threonine 231 in Creutzfeldt–Jakob disease

Büerger

Otto

Teipel

et al. 2006

Neurobiology of Aging

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“…Deposition of both PrP sc and Ain the central nervous system (CNS) results in neurodegeneration. Moreover, the coexistence of Aand PrP sc amyloid deposits in affected brains, although controversial, has been widely reported (Barcikowska et al, 1995;Debatin et al, 2008;Ferrer et al, 2001;Hainfellner et al, 1998;Leuba et al, 2000;Tsuchiya et al, 2004). In addition, a recent study indicates that PrP c may participate in the removal of A oligomers, which would implicate PrP c in AD (Charveriat et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Involvement of Dab1 in APP processing and β-amyloid deposition in sporadic Creutzfeldt–Jakob patients

Gavı́n¹,

Ferrer²,

Rı́o³

2010

Neurobiology of Disease

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Alzheimer's disease and prion pathologies (e.g., Creutzfeldt-Jakob disease (CJD)) display profound neural lesions associated with aberrant protein processing and extracellular amyloid deposits. Dab1 has been implicated in the regulation of Amyloid Precursor Protein (APP), but a direct link between human prion diseases and Dab1/APP interactions has not been published. Here we examined this putative relationship in seventeen cases of sporadic CJD (sCJD) post mortem. Biochemical analyses of brain tissue revealed two groups, which also correlated with PrP sc types 1 and 2. One group, with PrP sc type 1 showed increased Dab1 phosphorylation, and lower CTF production with an absence of A deposition. The second sCJD group, which carried PrP sc type 2, showed lower levels of Dab1 phosphorylation and CTF production, and A deposition. Thus, the present observations suggest a correlation between Dab1-phosphorylation, A deposition and PrP sc type in sCJD.

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“…AD and CJD share a variety of neuropathological features (7)(8)(9), and the Val/Met-129 polymorphism in the gene encoding PrP C has been identified as a risk factor for early onset AD (10,11). In addition, like APP, PrP C is shed from the cell surface by zinc metalloproteases and is subject to endoproteolysis by ADAM10 and ADAM17 (12)(13)(14)(15).…”

mentioning

confidence: 99%

Cellular prion protein regulates β-secretase cleavage of the Alzheimer's amyloid precursor protein

Parkin

Watt²,

Hussain³

et al. 2007

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

255

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Proteolytic processing of the amyloid precursor protein (APP) by ␤-secretase, ␤-site APP cleaving enzyme (BACE1), is the initial step in the production of the amyloid ␤ (A␤) peptide, which is involved in the pathogenesis of Alzheimer's disease. The normal cellular function of the prion protein (PrP C ), the causative agent of the transmissible spongiform encephalopathies such as CreutzfeldtJakob disease in humans, remains enigmatic. Because both APP and PrP C are subject to proteolytic processing by the same zinc metalloproteases, we tested the involvement of PrP C in the proteolytic processing of APP. Cellular overexpression of PrP C inhibited the ␤-secretase cleavage of APP and reduced A␤ formation. Conversely, depletion of PrP C in mouse N2a cells by siRNA led to an increase in A␤ peptides secreted into the medium. In the brains of PrP knockout mice and in the brains from two strains of scrapieinfected mice, A␤ levels were significantly increased. Two mutants of PrP, PG14 and A116V, that are associated with familial human prion diseases failed to inhibit the ␤-secretase cleavage of APP. Using constructs of PrP, we show that this regulatory effect of PrP C on the ␤-secretase cleavage of APP required the localization of PrP C to cholesterol-rich lipid rafts and was mediated by the N-terminal polybasic region of PrP C via interaction with glycosaminoglycans. In conclusion, this is a mechanism by which the cellular production of the neurotoxic A␤ is regulated by PrP C and may have implications for both Alzheimer's and prion diseases.lipid raft ͉ proteolysis ͉ scrapie ͉ glycosaminoglycan A lzheimer's disease (AD) is characterized by the presence of extracellular senile plaques and intracellular neurofibrillary tangles within the afflicted brain. The major constituents of senile plaques are the amyloid ␤ (A␤) peptides, which are derived from the proteolytic processing of the amyloid precursor protein (APP) (1). In the amyloidogenic pathway, ␤-secretase cleavage of APP yields a soluble N-terminal fragment sAPP␤, along with a short membrane-bound C-terminal fragment that is subsequently cleaved by ␥-secretase to release the A␤ peptides. In the alternative, nonamyloidogenic pathway, ␣-secretase cleaves APP within the A␤ sequence, thus precluding the formation of A␤, and releases a soluble N-terminal fragment sAPP␣. The transmembrane aspartyl protease, ␤-site APP cleaving enzyme (BACE1), has been identified as ␤-secretase (2), members of the ADAM (a disintegrin and metalloprotease) family, particularly ADAM10 and ADAM17, are responsible for ␣-secretase cleavage (3), while a complex of at least four proteins, the presenilins, nicastrin, Aph-1, and Pen-2, constitutes the ␥-secretase (2).The prion protein (PrP) is the causative agent of the transmissible spongiform encephalopathies (TSEs) that include CreutzfeldtJakob disease (CJD), Gerstmann-Scheinker-Straussler (GSS) disease, kuru and fatal familial insomnia in humans, bovine spongiform encephalopathy in cattle, and scrapie in sheep (4). In these diseases, the normal ce...

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Coexistence of Alzheimer-type neuropathology in Creutzfeldt-Jakob disease

Cited by 133 publications

References 20 publications

Dissociation between CSF total tau and tau protein phosphorylated at threonine 231 in Creutzfeldt–Jakob disease

Dissociation between CSF total tau and tau protein phosphorylated at threonine 231 in Creutzfeldt–Jakob disease

Involvement of Dab1 in APP processing and β-amyloid deposition in sporadic Creutzfeldt–Jakob patients

Cellular prion protein regulates β-secretase cleavage of the Alzheimer's amyloid precursor protein

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