Interestingly, both PD and incidental Lewy body disease tissues showed 100% concordance for elevated levels of pathological α-synuclein seeding activity compared to control tissues.
This study highlights the therapeutic potential of α-synuclein immunotherapy for the treatment of PD and DLB, and provides a framework for screening of α-synuclein antibodies to identify those with preferred properties.
They expressed truncated, oligomeric and proteinase K-resistant phosphorylated forms of α-synuclein in the regions that are specifically affected in Parkinson's disease and/or dementia with Lewy bodies, including the olfactory bulb, cerebral cortex, striatum and substantia nigra.
One of the pathological proteins, alpha-synuclein (α-syn), accumulates in the brains of Parkinson disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), which are designated as synucleinopathies.
PD, PD with dementia, and dementia with Lewy bodies are clinical syndromes characterized by the neuropathological accumulation of alpha-synuclein in the CNS that represent a clinicopathological spectrum known as Lewy body disorders.
Since the observation of its relation to PD, GBA1 mutations have become recognized as the most common genetic risk factor for development of synucleinopathies such as PD and dementia with Lewy bodies.
Mutations in the gene glucocerebrosidase (GBA1) are specifically associated with alpha-synucleinopathies, namely, Parkinson's disease (PD) and dementia with Lewy bodies.
A cerebrospinal fluid (CSF) biomarker panel for AD is making its way into the clinic, but an equivalent panel for PD and DLB and for improved differential diagnoses is still lacking.
To study the influence of concomitant Alzheimer's disease (AD) pathology in dementia with Lewy bodies (DLB) on dopamine transporter (DAT) and serotonin transporter (SERT) availability, using <sup>123</sup>I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (<sup>123</sup>I-FP-CIT) single photon emission computed tomography (SPECT).
Over the last 20 years, many neurophysiological, neuroimaging, and cerebrospinal fluid (CSF) biomarkers have been described toward a better discrimination between dementia with Lewy bodies, Alzheimer disease, and other neurodegenerative conditions.In the present review, we aim to describe the neurophysiological, imaging, and CSF biomarkers in dementia with Lewy bodies and to question whether they could be reliable tools for the clinical practice.
Reduced uptake in dopamine transporter imaging and reduced myocardial uptake in iodine-123 metaiodobenzylguanidine cardiac scintigraphy are indicative biomarkers for DLB diagnosis.
The algorithm includes baseline clinical and cognitive assessment, blood examination, and magnetic resonance imaging with exclusionary and inclusionary roles; dopamine transporter single-photon emission computed tomography (if no/unclear parkinsonism) or metaiodobenzylguanidine cardiac scintigraphy for suspected dementia with Lewy bodies with clear parkinsonism (round VII, votes (yes-no-abstained): 3-1-1); <sup>18</sup> F-fluorodeoxyglucose positron emission tomography for suspected frontotemporal lobar degeneration and low diagnostic confidence of Alzheimer's disease (round VII, 4-0-1); cerebrospinal fluid for suspected Alzheimer's disease (round IV, 4-1-0); and amyloid positron emission tomography if cerebrospinal fluid was not possible/accepted (round V, 4-1-0) or inconclusive (round VI, 5-0-0).
A cerebrospinal fluid (CSF) biomarker panel for AD is making its way into the clinic, but an equivalent panel for PD and DLB and for improved differential diagnoses is still lacking.
Over the last 20 years, many neurophysiological, neuroimaging, and cerebrospinal fluid (CSF) biomarkers have been described toward a better discrimination between dementia with Lewy bodies, Alzheimer disease, and other neurodegenerative conditions.In the present review, we aim to describe the neurophysiological, imaging, and CSF biomarkers in dementia with Lewy bodies and to question whether they could be reliable tools for the clinical practice.
To investigate whether acetylcholinesterase inhibitor (AChEI) use prevents or delays subsequent initiation of psychotropic medications in people with Alzheimer's disease (AD) and Lewy body dementia (LBD).
We also found that downstream pre-synaptic dopamine D1 Receptor binding correlated with dopamine loss in Lewy body disease groups, and RNA damage and β-site APP cleaving enzyme 1 in the caudate of AD.
Our study suggests that catD upregulation may be an adaptive response to AD-related processes leading to neurofibrillary degeneration, but may not be directly associated with formation of α-synuclein inclusions in Lewy body dementia.
The patients with Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies whose brain pathology indicated deposit of alpha-synuclein along with the co-occurrence of tau pathology and amyloid-beta plaques presented LRP10 mutations.
Although the mechanisms through which glucocerebrosidase regulates the homeostasis of α-synuclein remains poorly understood, the identification of reduced glucocerebrosidase activity in the brains of patients with PD and dementia with Lewy bodies has paved the way for the development of novel therapeutic strategies directed at enhancing glucocerebrosidase activity and reducing α-synuclein burden, thereby slowing down or even preventing neuronal death.
α-Synuclein is the most thoroughly investigated because of its close association with Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy.