CSF levels of the BACE1 substrate NRG1 correlate with cognition in Alzheimer's disease.

Alzheimer's Research & Therapy
François Mouton-LigerClaire Paquet

Abstract

The presynaptic protein neuregulin1 (NRG1) is cleaved by beta-site APP cleaving enzyme 1 (BACE1) in a similar way as amyloid precursor protein (APP) NRG1 can activate post-synaptic receptor tyrosine-protein kinase erbB4 (ErbB4) and was linked to schizophrenia. The NRG1/ErbB4 complex is neuroprotective, can trigger synaptogenesis and plasticity, increases the expression of NMDA and GABA receptors, and can induce neuroinflammation. This complex can reduce memory formation. In Alzheimer's disease (AD) brains, NRG1 accumulates in neuritic plaques. It is difficult to determine if NRG1 has beneficial and/or detrimental effects in AD. BACE1 levels are increased in AD brains and cerebrospinal fluid (CSF) and may lead to enhanced NRG1 secretion, but no study has assessed CSF NRG1 levels in AD and mild cognitive impairment (MCI) patients. This retrospective study included 162 patients suffering from AD dementia (54), MCI with progression to AD dementia (MCI-AD) (27), non-AD MCI (30), non-AD dementias (30), and neurological controls (27). All patients had neurological examinations, brain MRI, and neuropsychological evaluations. After written informed consent and using enzyme-linked immunosorbent assays (ELISAs), CSF samples were evaluated...Continue Reading

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Citations

Oct 21, 2020·Biomedicines·Adrian Florian BălașaAlexandru Mihai Grumezescu
Dec 5, 2020·BioMed Research International·Xiaoling WangJialei Xu
Mar 3, 2021·European Journal of Medicinal Chemistry·Sukriti SrivastavaSunil Kumar Khare

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Methods Mentioned

BETA
ELISA
BACE

Software Mentioned

SAS

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