Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Aberrant Wnt signaling pathway in medial temporal lobe structures of Alzheimer's disease

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Author Correction: Assessment of brain reference genes for RT-qPCR studies in neurodegenerative diseases

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s Disease

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Authors' response: Association between IBD and Parkinson's disease: seek and you shall find?

    Publikation: Bidrag til tidsskriftKommentar/debatForskning

  5. Misfolded SOD1 inclusions in patients with mutations in C9orf72 and other ALS/FTD-associated genes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Cognitive decline is a cardinal feature of Alzheimer's disease (AD) predominantly linked to synaptic failure, disrupted network connectivity and neurodegeneration. A large body of evidence associates the Wnt pathway with synaptic modulation and cognitive processes, suggesting a potential role for aberrant Wnt signaling in cognitive impairment. In fact, altered expression of key Wnt pathway components has been found in brains of AD patients as well as AD animal models supporting a deregulated pathway in AD. The evidence for deregulated Wnt signaling in AD, however, remains sparse and focused on isolated Wnt pathway components. Here, we provide the first comprehensive pathway-focused evaluation of the Wnt pathway in the entorhinal cortex and hippocampus of AD brains. Our data demonstrate altered Wnt pathway gene expression at all levels of the pathway in both medial temporal lobe regions with the hippocampus exhibiting most pronounced changes. Furthermore, the Wnt pathway constituents Wnt7b and Tcf7l1/Tcf3 showed overlapping gene expression alterations across both medial temporal lobe structures, while β-catenin was inversely expressed between brain regions. We also identified total protein alterations of the intracellular Wnt pathway signaling components β-catenin, Gsk3β and Tcf7l1/Tcf3 and the phosphorylation state of β-catenin and Gsk3β in the hippocampus suggestive of a link between AD and aberrant canonical activity. Alterations in Gsk3β co-appeared with hippocampal kinase-targeted hyperphosphorylation at specific tau epitope in soluble pretangles and prominent tau aggregation exclusively in insoluble neurofibrillary tangles of AD subjects. The Wnt pathway-focused approach confirms altered Wnt signaling in the neurodegenerative AD brain and highlights the potential role of the pathway as a therapeutic target for the treatment of patients.

OriginalsprogEngelsk
TidsskriftJournal of neural transmission (Vienna, Austria : 1996)
Vol/bind122
ISSN0300-9564
DOI
StatusUdgivet - 14 feb. 2015

ID: 44985572