Patient with corticobasal syndrome showing disease-associated biomarkers of dementia with Lewy Bodies: a Treviso Dementia (TREDEM) registry case report

Background: An 82-year-old right-handed man, a retired teacher, reported the occurrence, three years earlier, of difficulties in moving his left arm and foot, tremor in his left hand, and gestures of the left upper limb that appeared to be independent of the patient's will.Objective: We describe an unusual case of corticobasal syndrome (CBS) showing disease-associated biomarkers of dementia with Lewy bodies (DLB).Methods: Clinical, neuropsychological, imaging, and biomarker evaluations were conducted, including tau and amyloid-beta levels in the cerebrospinal fluid (CSF) and a RT-QuIC assay for alpha-synuclein both in the CSF and olfactory mucosa (OM), as well as a QEEG assessment.Results: The patient presented resting tremor, mild extrapyramidal hypertonus, mild bradykinesia on the left side, and severe apraxia on the left upper limb. Brain MRI showed a diffuse right hemisphere atrophy which was prominent in the posterior parietal and temporal cortices, and moderate in the frontal cortex and the precuneus area. F-18-FDG PET imaging showed reduced glucose metabolism in the right lateral parietal, temporal, and frontal cortices with involvement of the right precuneus. The putamen did not appear to be pathological at DaTQUANT. Neuropsychological tests showed memory and visual-perceptual deficits. CSF tau and amyloid measurements did not show clear pathological values. RT-QuIC for alpha-synuclein in CSF and OM samples were positive. The QEEG analysis showed a pre-alpha dominant frequency in posterior derivations, typical of early stages of DLB.Conclusion: Although in the present patient the clinical diagnosis was of probable CBS, unexpectedly positive biomarkers for DLB suggested the co-presence of multiple pathologies

Neural progenitor cells orchestrate microglia migration and positioning into the developing cortex

Microglia are observed in the early developing forebrain and contribute to the regulation of neurogenesis through still unravelled mechanisms. In the developing cerebral cortex, microglia cluster in the ventricular/subventricular zone (VZ/SVZ), a region containing Cxcl12-expressing basal progenitors (BPs). Here we show that the ablation of BP as well as genetic loss of Cxcl12 affect microglia recruitment into the SVZ. Ectopic Cxcl12 expression or pharmacological blockage of CxcR4 further supports that Cxcl12/CxcR4 signalling is involved in microglial recruitment during cortical development. Furthermore, we found that cell death in the developing forebrain triggers microglial proliferation and that this is mediated by the release of macrophage migration inhibitory factor (MIF). Finally, we show that the depletion of microglia in mice lacking receptor for colony-stimulating factor-1 (Csf-1R) reduces BPs into the cerebral cortex