Abstract
BackgroundParkinson’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.MethodsHere, 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.ResultsWe found that p-APPT668 (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-LRRK2S935 are all elevated in PDD compared to control. Interestingly, protein levels of p-TauS199/202 in CP and DD2R, DRP1, and VPS35 in TC are all increased in PDD compared to DLB.ConclusionsTogether, 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.
Highlights
Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are common age-related neurode‐ generative diseases comprising Lewy body spectrum disorders associated with cortical and subcortical Lewy body pathology
Together, our comprehensive and systematic study identified a set of signature proteins that will help to understand the pathology and etiology of PD dementia (PDD) and Dementia with Lewy bodies (DLB) at the molecular level
According to the clinical diagnosis, including disease history, clinical presentation, dementia scores, alpha-synuclein pathological feature, and phosphor-Tau- and Aβ-related pathological features, the cases were classified as the control, PDD, and DLB patients by their clinical doctors (Additional file 1: Table S1), which were used as the three study groups investigated here
Summary
Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are common age-related neurode‐ generative diseases comprising Lewy body spectrum disorders associated with cortical and subcortical Lewy body pathology. While PDD and DLB share similar pathological substrates, they differ in the temporal onset of motor and cognitive symptoms; protein markers to distinguish them are still lacking. Parkinson’s disease (PD) is a chronic neurodegenerative movement disorder characterized clinically by limb rigidity, bradykinesia, tremor, and postural instability. 30% of PD patients have mild cognitive symptoms at the time of motor symptom onset, and approximately 80% will develop Parkinson’s disease. Dementia with Lewy bodies (DLB) is characterized by the deposition of Lewy bodies, which contain abnormally folded α-synuclein in neurons. PDD and DLB comprise Lewy body dementia (LBD) spectrum disorders associated with cortical and subcortical Lewy body pathology
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