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.
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).
Study Type
OBSERVATIONAL
Enrollment
80
Klinik und Poliklinik für Psychiatrie und Psychotherapie des LMU Klinikums
München, Bavaria, Germany
RECRUITINGDisruption of the brain-blood-barrier between the subgroups
Name of Measurement: Ktrans; Measurement Tool: dynamic contrast imaging(DCI) sequence (MRI); Unit: min -1
Time frame: Baseline
Clearance mechanisms and glymphatic or cerebral lymphatic system
Name of Measurement: Diffusion tensor imaging (DTI) Analysis along the perivascular space (ALPS); Measurement Tool: DTI MRI; Unit: mean (Dxpro, Dypro)/ mean (Dypro, Dzasc)
Time frame: Baseline
Changes in circadian rhythms
Sleep Efficiency, proportional integration mode (PIM) ;Measurement Tool: Actigraphy; Units: counts
Time frame: Baseline
Correlation between clinical symptoms, tau pathology and BBB disorder
Correlations between neuropsychological tests (e.g. Clinical Dementia Rating Sum of Boxes), CSF markers (pg/ml) and TAU PET, standardized uptake value ratio (SUVr) and Ktrans map
Time frame: Baseline
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