Neuroligin-1 in brain and CSF of neurodegenerative disorders: investigation for synaptic biomarkers

Acta Neuropathologica Communications

Oskar Hansson¹  Johan Gobom²  Elena Camporesi²  Kaj Blennow²  Bruno Becker²  Juan Lantero-Rodriguez²  Henrik Zetterberg³  Tammaryn Lashley⁴ 

[1] Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden;Memory Clinic, Skåne University Hospital, Malmö, Sweden;Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy At University of Gothenburg, Mölndal, Sweden;Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden;Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy At University of Gothenburg, Mölndal, Sweden;Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden;Dementia Research Institute At UCL, London, UK;Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK;The Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, London, UK;Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, Queen Square, London, UK;

关键词: Neuroligin-1;    Synapse loss;    Alzheimer’s disease;    Tauopathies;   

DOI  :  10.1186/s40478-021-01119-4

来源: Springer

【 摘 要 】

Synaptic pathology is a central event in Alzheimer’s disease (AD) and other neurodegenerative conditions, and investigation of synaptic proteins can provide valuable tools to follow synaptic dysfunction and loss in these diseases. Neuroligin-1 (Nlgn1) is a postsynaptic cell adhesion protein, important for synapse stabilization and formation. Nlgn1 has been connected to cognitive disorders, and specifically to AD, as target of the synaptotoxic effect of amyloid-β (Aβ) oligomers and Aβ fibrils. To address changes in Nlgn1 expression in human brain, brain regions in different neurological disorders were examined by Western blot and mass spectrometry. Brain specimens from AD (n = 23), progressive supranuclear palsy (PSP, n = 11), corticobasal degeneration (CBD, n = 10), and Pick’s disease (PiD, n = 9) were included. Additionally, cerebrospinal fluid (CSF) samples of AD patients (n = 43) and non-demented controls (n = 42) were analysed. We found decreased levels of Nlgn1 in temporal and parietal cortex (~ 50–60% reductions) in AD brains compared with controls. In frontal grey matter the reduction was not seen for AD patients; however, in the same region, marked reduction was found for PiD (~ 77%), CBD (~ 66%) and to a lesser extent for PSP (~ 43%), which could clearly separate these tauopathies from controls. The Nlgn1 level was reduced in CSF from AD patients compared to controls, but with considerable overlap. The dramatic reduction of Nlgn1 seen in the brain extracts of tauopathies warrants further investigation regarding the potential use of Nlgn1 as a biomarker for these neurodegenerative diseases.

【 授权许可】

CC BY