Distribution of cholinergic nerve terminals in the aged human brain measured with [F]FEOBV PET and its correlation with histological data.

Introduction: [F]fluoroetoxybenzovesamicol ([F]FEOBV) is a positron emission topography (PET) tracer for the vesicular acetylcholine transporter (VAChT), a protein located predominantly in synaptic vesicles in cholinergic nerve terminals. We aimed to use [F]FEOBV PET to study the cholinergic topography of the healthy human brain.

Materials And Methods: [F]FEOBV PET brain data volumes of healthy elderly humans were normalized to standard space and intensity-normalized to the white matter.

A postmortem study suggests a revision of the dual-hit hypothesis of Parkinson's disease.

The dual-hit hypothesis of Parkinson's disease (PD) originally postulated that a neurotropic pathogen leads to formation of α-synuclein pathology in the olfactory bulb (OB) and dorsal motor nucleus of the vagus (DMV) and then invades the brain from these two entry points. Little work has been conducted to validate an important underlying premise for the dual-hit hypothesis, namely that the initial Lewy pathology does arise simultaneously in the OB and the enteric nervous system (ENS) plexuses and DMV at the earliest disease stage. We conducted a focused re-analysis of two postmortem datasets, which included large numbers of mild Lewy body disease (LBD) cases.

Impact of aging on animal models of Parkinson's disease.

Aging is the biggest risk factor for developing Parkinson's disease (PD), the second most common neurodegenerative disorder. Several animal models have been developed to explore the pathophysiology underlying neurodegeneration and the initiation and spread of alpha-synuclein-related PD pathology, and to investigate biomarkers and therapeutic strategies. However, bench-to-bedside translation of preclinical findings remains suboptimal and successful disease-modifying treatments remain to be discovered.

Alpha-Synuclein Strain Variability in Body-First and Brain-First Synucleinopathies.

Pathogenic alpha-synuclein (asyn) aggregates are a defining feature of neurodegenerative synucleinopathies, which include Parkinson's disease, Lewy body dementia, pure autonomic failure and multiple system atrophy. Early accurate differentiation between these synucleinopathies is challenging due to the highly heterogeneous clinical profile at early prodromal disease stages. Therefore, diagnosis is often made in late disease stages when a patient presents with a broad range of motor and non-motor symptoms easing the differentiation.