Compta, Y;
Revesz, T;
(2020)
Neuropathological and Biomarker Findings in Parkinson's Disease and Alzheimer's Disease: From Protein Aggregates to Synaptic Dysfunction.
Journal of Parkinson's Disease
10.3233/JPD-202323.
(In press).
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Abstract
There is mounting evidence that Parkinson’s disease (PD) and Alzheimer’s disease (AD) share neuropathological hallmarks, while similar types of biomarkers are being applied to both. In this review we aimed to explore similarities and differences between PD and AD at both the neuropathology and the biomarker levels, specifically focusing on protein aggregates and synapse dysfunction. Thus, amyloid- peptide (A) and tau lesions of the Alzheimer-type are common in PD and -synuclein Lewy-type aggregates are frequent findings in AD. Modern neuropathological techniques adding to routine immunohistochemistry might take further our knowledge of these diseases beyond protein aggregates and down to their presynaptic and postsynaptic terminals, with potential mechanistic and even future therapeutic implications. Translation of neuropathological discoveries to the clinic remains challenging. Cerebrospinal fluid (CSF) and positron emission tomography (PET) markers of A and tau have been shown to be reliable for AD diagnosis. Conversely, CSF markers of -synuclein have not been that consistent. In terms of PET markers, there is no PET probe available for -synuclein yet, while the AD PET markers range from consistent evidence of their specificity (amyloid imaging) to greater uncertainty of their reliability due to off-target binding (tau imaging). CSF synaptic markers are attractive, still needing more evidence, which currently suggests those might be non-specific markers of disease progression. It can be summarized that there is neuropathological evidence that protein aggregates of AD and PD are present both at the soma and the synapse. Thus, a number of CSF and PET biomarkers beyond -synuclein, tau and A might capture these different faces of protein-related neurodegeneration. It remains to be seen what the longitudinal outcomes and the potential value as surrogate markers of these biomarkers are.
| Type: | Article |
|---|---|
| Title: | Neuropathological and Biomarker Findings in Parkinson's Disease and Alzheimer's Disease: From Protein Aggregates to Synaptic Dysfunction |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3233/JPD-202323 |
| Publisher version: | https://doi.org/10.3233/JPD-202323 |
| Language: | English |
| Additional information: | This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0). https://creativecommons.org/licenses/by-nc/4.0/ |
| Keywords: | α-Synuclein, alzheimer’s disease, amyloid-, biomarkers, cerebrospinal fluid, lewy-type pathology, molecular imaging, Parkinson’s disease, synaptic dysfunction, tau |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10118952 |
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