Clearance Mechanisms in Atypical Neurodegenerative Diseases — PeptiClear  

Neurodegenerative Diseases Clinical Trial

Official title: Cerebral Clearance Mechanisms in Atypical Neurodegenerative Diseases: A Multi-modal Study on Lymphatic, Glymphatic and Blood-brain-barrier Function

Status Recruiting

Clinical Trial Summary

The project PeptiClear aims to investigate whether the blood-brain-barrier (BBB) and the glymphatic system are compromised in atypical neurodegenerative diseases, and whether Alzheimer´s disease (AD)-related copathology, vascular lesions or sleep disturbances modify the clinical picture or structural and/or functional features of the diseases.

Clinical Trial Description

It is well established for the frequent sporadic (non-genetic) variant of Alzheimer´s disease (AD) that not the overproduction of a specific protein (Amyloid-beta - Aβ) is a major cause but rather the insufficient clearance of this protein from the central nervous system. On one hand, under physiological conditions, the interplay of the several cell types (cerebral endothelial cells, perivascular mural cells (pericytes), glial cells (astrocytes and microglia) and neurons) regulates the neuronal and glial cell environment and is crucial for cell function and survival. On the other hand, Aβ aggregates lead to BBB damage and activation of microglial cells. The BBB facilitates the clearance of proteins such as Aβ via the cerebrovascular system, but its association with other intracerebral Aβ drainage systems, such as the glympathic system, remains to be clarified. As the glymphatic system is mainly active during sleep, sleep disturbances could influence the clinical course. Concerning atypical neurodegenerative diseases, it is not clear whether tau or alpha-synuclein (alpha-syn) deposits also have a potential to damage the BBB. In AD Aβ aggregation and vascular changes give rise to insufficient protein clearance and thus contribute to AD pathogenesis in a synergistic fashion. However the role of copathology in atypical neurodegenerative diseases - which mainly consists of Alzheimer-related changes and vascular pathology - is elusive and remains to be clarified.

The prospective study cohort (N ~80) will include patients with Lewy Body spectrum disease, progressive supranuclear palsy, corticobasal syndrome and frontotemporal dementia. All study participants will undergo a detailed clinical and neuropsychological assessment according to a standardised protocol (i.a. magnet resonance imaging (MRI), positron emission tomography (PET), cerebrospinal fluid (CSF), actigraphy). ;

Related Conditions & MeSH terms

• Frontotemporal Degeneration
• Neurodegenerative Diseases

• NCT number: NCT05317871
• Study type: Observational
• Source: Ludwig-Maximilians - University of Munich
• Contact: Robert Perneczky, Prof. Dr.
• Phone: +4989440055863
• Email: PSY.Alzheimerzentrum@med.uni-muenchen.de
• Status: Recruiting
• Start date: April 1, 2022
• Completion date: April 2024