Post-mortem brain analyses of the Lothian Birth Cohort 1936: extending lifetime cognitive and brain phenotyping to the level of the synapse

Acta Neuropathologica Communications
Christopher M HenstridgeTara L Spires-Jones

Abstract

Non-pathological, age-related cognitive decline varies markedly between individuals andplaces significant financial and emotional strain on people, their families and society as a whole.Understanding the differential age-related decline in brain function is critical not only for the development oftherapeutics to prolong cognitive health into old age, but also to gain insight into pathological ageing suchas Alzheimer's disease. The Lothian Birth Cohort of 1936 (LBC1936) comprises a rare group of people forwhom there are childhood cognitive test scores and longitudinal cognitive data during older age, detailedstructural brain MRI, genome-wide genotyping, and a multitude of other biological, psycho-social, andepidemiological data. Synaptic integrity is a strong indicator of cognitive health in the human brain;however, until recently, it was prohibitively difficult to perform detailed analyses of synaptic and axonalstructure in human tissue sections. We have adapted a novel method of tissue preparation at autopsy toallow the study of human synapses from the LBC1936 cohort in unprecedented morphological andmolecular detail, using the high-resolution imaging techniques of array tomography and electronmicroscopy. This allows us to ana...Continue Reading

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Citations

Apr 3, 2016·Acta Neuropathologica Communications·Ksenia KurbatskayaWendy Noble
Apr 25, 2016·Ageing Research Reviews·Christopher M HenstridgeTara L Spires-Jones
Sep 11, 2018·International Journal of Stroke : Official Journal of the International Stroke Society·Catherine A HumphreysColin Smith
Dec 19, 2018·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Jill R GlausierDavid A Lewis
Mar 17, 2018·International Journal of Epidemiology·Adele M TaylorIan J Deary
Dec 24, 2017·Acta Neuropathologica·Christopher M HenstridgeTara L Spires-Jones
Jan 16, 2019·Nature Reviews. Neuroscience·Christopher M HenstridgeTara L Spires-Jones
May 15, 2021·Nature Reviews. Disease Primers·David S KnopmanDavid T Jones
Aug 1, 2021·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·Hatice KurucuTara L Spires-Jones

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Methods Mentioned

BETA
electron microscopy
dissection
protein assay
dissector
transmission electron microscopy
pharmacotherapy
genotyping

Software Mentioned

GraphPad Prism
Odyssey
AxioImager
SPSS
MATLAB
MATLAB scripts
ImageJ
Stereo Investigator

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