In:
BMC Neuroscience, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-12)
Abstract:
Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are common age-related neurodegenerative diseases comprising Lewy body spectrum disorders associated with cortical and subcortical Lewy body pathology. Over 30% of PD patients develop PD dementia (PDD), which describes dementia arising in the context of established idiopathic PD. Furthermore, Lewy bodies frequently accompany the amyloid plaque and neurofibrillary tangle pathology of Alzheimer’s disease (AD), where they are observed in the amygdala of approximately 60% of sporadic and familial AD. While PDD and DLB share similar pathological substrates, they differ in the temporal onset of motor and cognitive symptoms; however, protein markers to distinguish them are still lacking. Methods Here, we systematically studied a series of AD and PD pathogenesis markers, as well as mitochondria, mitophagy, and neuroinflammation-related indicators, in the substantia nigra (SN), temporal cortex (TC), and caudate and putamen (CP) regions of human post-mortem brain samples from individuals with PDD and DLB and condition-matched controls. Results We found that p-APP T668 (TC), α-synuclein (CP), and LC3II (CP) are all increased while the tyrosine hydroxylase (TH) (CP) is decreased in both PDD and DLB compared to control. Also, the levels of Aβ42 and DD2R, IBA1, and p-LRRK2 S935 are all elevated in PDD compared to control. Interestingly, protein levels of p-Tau S199/202 in CP and DD2R, DRP1, and VPS35 in TC are all increased in PDD compared to DLB. Conclusions Together, our comprehensive and systematic study identified a set of signature proteins that will help to understand the pathology and etiology of PDD and DLB at the molecular level.
Type of Medium:
Online Resource
ISSN:
1471-2202
DOI:
10.1186/s12868-021-00687-4
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2041344-0
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