Introduction: Neuroinflammation and synaptic degeneration are major neuropathological hallmarks in Alzheimer's disease (AD). Neurogranin and YKL-40 in cerebrospinal fluid (CSF) are newly discovered markers indicating synaptic damage and microglial activation, respectively.
Methods: CSF samples from 95 individuals including 39 patients with AD dementia (AD-D), 13 with mild cognitive impairment (MCI) due to AD (MCI-AD), 29 with MCI not due to AD (MCI-o) and 14 patients with non-AD dementias (non-AD-D) were analyzed for neurogranin and YKL-40.
Results: Patients with dementia or MCI due to AD showed elevated levels of CSF neurogranin (p < 0.001 for AD-D and p < 0.05 for MCI-AD) and YKL-40 (p < 0.05 for AD-D and p = 0.15 for MCI-AD) compared to mildly cognitively impaired subjects not diagnosed with AD. CSF levels of neurogranin and YKL-40 did not differ between MCI not due to AD and non-AD dementias. In AD subjects no correlation between YKL-40 and neurogranin was found. The CSF neurogranin levels correlated moderately with tau and p-tau but not with Aβ42 or the MMSE in AD samples. No relevant associations between YKL-40 and MMSE or the core AD biomarkers, Aβ42, t-tau and p-tau were found in AD subjects.
Conclusions: Neurogranin and YKL-40 are promising AD biomarkers, independent of and complementary to the established core AD biomarkers, reflecting additional pathological changes in the course of AD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690296 | PMC |
http://dx.doi.org/10.1186/s13195-015-0161-y | DOI Listing |
Parkinsonism Relat Disord
January 2025
Turku PET Centre, University of Turku, Turku, Finland; Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.
Objective: To investigate neuroinflammation in Parkinson's disease (PD) with [C]PBR28 positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers, and the relationship to dopaminergic functioning measured with 6-[F]-fluoro-L-dopa ([F]FDOPA) PET.
Methods: The clinical cohort consisted of 20 subjects with PD and 51 healthy controls (HC). All HC and 15 PD participants underwent [C]PBR28 High Resolution Research Tomograph (HRRT) PET for the quantitative assessment of cerebral binding to the translocator protein (TSPO), a neuroinflammation marker.
Brain Commun
October 2024
Alzheimer center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Programme Neurodegeneration, Amsterdam University Medical Centers, Vrije Universiteit, 1081 HZ Amsterdam, The Netherlands.
Expert Rev Neurother
November 2024
Division of Molecular Medicine, Ruder Boskovic Institute, Zagreb, Croatia.
Alzheimers Dement (N Y)
August 2024
Amylyx Pharmaceuticals, Inc. Cambridge Massachusetts USA.
Introduction: Sodium phenylbutyrate and taurursodiol (PB and TURSO) is hypothesized to mitigate endoplasmic reticulum stress and mitochondrial dysfunction, two of many mechanisms implicated in Alzheimer's disease (AD) pathophysiology.
Methods: The first-in-indication phase 2a PEGASUS trial was designed to gain insight into PB and TURSO effects on mechanistic targets of engagement and disease biology in AD. The primary clinical efficacy outcome was a global statistical test combining three endpoints relevant to disease trajectory (cognition [Mild/Moderate Alzheimer's Disease Composite Score], function [Functional Activities Questionnaire], and total hippocampal volume on magnetic resonance imaging).
Alzheimers Dement
August 2024
Wisconsin Alzheimer's Disease Research Center and Department of Geriatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Introduction: We examined whether the aging suppressor KLOTHO gene's functionally advantageous KL-VS variant (KL-VS heterozygosity [KL-VS]) confers resilience against deleterious effects of aging indexed by cerebrospinal fluid (CSF) biomarkers of neuroinflammation (interleukin-6 [IL-6], S100 calcium-binding protein B [S100B], triggering receptor expressed on myeloid cells [sTREM2], chitinase-3-like protein 1 [YKL-40], glial fibrillary acidic protein [GFAP]), neurodegeneration (total α-synuclein [α-Syn], neurofilament light chain protein), and synaptic dysfunction (neurogranin [Ng]).
Methods: This Alzheimer disease risk-enriched cohort consisted of 454 cognitively unimpaired adults (M= 61.5 ± 7.
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