SET translocation is associated with increase in caspase cleaved amyloid precursor protein in CA1 of Alzheimer and Down syndrome patients

Topic: Brain proteins, microglia and lab models

Caspase cleaved amyloid precursor protein (APPcc) and SET are increased and mislocalized in the neuronal cytoplasm in Alzheimer Disease (AD) brains. Translocated SET to the cytoplasm can induce tau hyperphosphorylation. To elucidate the putative relationships between mislocalized APPcc and SET, we studied their level and distribution in the hippocampus of 5 controls, 3 Down syndrome and 10 Alzheimer patients. In Down syndrome and Alzheimer patients, APPcc and SET levels were increased in CA1 and the frequency of both localizations in the neuronal cytoplasm was high in CA1, and low in CA4. As the increase of APPcc is already present at early stages of AD, we overexpressed APPcc in CA1 and the dentate gyrus neurons of adult mice with a lentiviral construct. APPcc overexpression in CA1 and not in the dentate gyrus induced endogenous SET translocation and tau hyperphosphorylation. These data suggest that increase in APPcc in CA1 neurons could be an early event leading to the translocation of SET and the progression of AD through tau hyperphosphorylation.

Key findings

• These data suggest that increase in APPcc in CA1 neurons could be an early event leading to the translocation of SET and the progression of AD through tau hyperphosphorylation.

Why it matters

In brain tissue from a small number of Alzheimer and Down syndrome patients, and in mice, increased caspase cleaved amyloid precursor protein in one hippocampal region was linked to SET translocation and tau hyperphosphorylation. This suggests a possible early step in disease progression, but no treatment, cure or prevention is demonstrated.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/j.neurobiolaging.2013.08.039
• PubMed: 24262202
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{facchinetti2014-24262202,
  author  = {Facchinetti, P. and Dorard, E. and Contremoulins, V. and Gaillard, M. C. and Déglon, N. and Sazdovitch, V. and Guihenneuc-Jouyaux, C. and Brouillet, E. and others},
  title   = {{SET translocation is associated with increase in caspase cleaved amyloid precursor protein in CA1 of Alzheimer and Down syndrome patients}},
  journal = {Neurobiology of aging},
  year    = {2014},
  doi     = {10.1016/j.neurobiolaging.2013.08.039},
  pmid    = {24262202},
  url     = {https://doi.org/10.1016/j.neurobiolaging.2013.08.039}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Phases of Aβ-deposition in the human brain and its relevance for the development of AD Neurology · 2002-06-25 · usefulness score 59/100 · Brain tissue and pathology
• Neuropathological stageing of Alzheimer-related changes Acta Neuropathologica · 1991-09-01 · usefulness score 58/100 · Brain tissue and pathology
• Reversal of Alzheimer's-like pathology and behavior in human APP transgenic mice by mutation of Asp664 Proceedings of the National Academy of Sciences of the United States of America · 2006-04-25 · usefulness score 49/100 · Risk genes beyond APOE

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• mTOR in Down syndrome: Role in Aß and tau neuropathology and transition to Alzheimer disease-like dementia Free radical biology & medicine · 2017-08-12 · usefulness score 45/100 · Down syndrome and Alzheimer's
• Increases of SET level and translocation are correlated with tau hyperphosphorylation at ser202/thr205 in CA1 of Ts65Dn mice Neurobiology of aging · 2016-06-23 · usefulness score 36/100 · Down syndrome and Alzheimer's

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• Mapping of the gene encoding the beta-amyloid precursor protein and its relationship to the Down syndrome region of chromosome 21 Proceedings of the National Academy of Sciences of the United States of America · 1988-11-01 · usefulness score 44/100
• Influence of the amyloid precursor protein locus on dementia in Down syndrome Neurology · 2004-06-01 · usefulness score 43/100

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