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Effect of Dietary Ketosis and Nicotinamide Riboside on Hippocampal Krebs Cycle Intermediates and Mitochondrial Energetics in a DNA Repair-Deficient 3xTg/POLβ Alzheimer Disease Mouse Model.
J Neurochem
January 2025
The Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Alzheimer disease is a neurodegenerative pathology-modifying mitochondrial metabolism with energy impairments where the effects of biological sex and DNA repair deficiencies are unclear. We investigated the therapeutic potential of dietary ketosis alone or with supplemental nicotinamide riboside (NR) on hippocampal intermediary metabolism and mitochondrial bioenergetics in older male and female wild-type (Wt) and 3xTgAD-DNA polymerase-β-deficient (3xTg/POLβ) (AD) mice. DNA polymerase-β is a key enzyme in DNA base excision repair (BER) of oxidative damage that may also contribute to mitochondrial DNA repair.
View Article and Find Full Text PDFDeficiency of histamine H receptors in parvalbumin-positive neurons leads to hyperactivity, impulsivity, and impaired attention.
Neuron
January 2025
Department of Pharmacology and Department of Pharmacy of the Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address:
Attention deficit hyperactivity disorder (ADHD), affecting 4% of the population, is characterized by inattention, hyperactivity, and impulsivity; however, its neurophysiological mechanisms remain unclear. Here, we discovered that deficiency of histamine H receptor (HR) in parvalbumin-positive neurons in substantia nigra pars recticulata (PV) attenuates PV neuronal activity and induces hyperactivity, impulsivity, and inattention in mice. Moreover, decreased HR expression was observed in PV in patients with ADHD symptoms and dopamine-transporter-deficient mice, whose behavioral phenotypes were alleviated by HR agonist treatment.
View Article and Find Full Text PDFBackground: Mild Cognitive Impairment (MCI) represents an intermediate stage between normal age-related cognitive decline and more severe degenerative conditions such as Alzheimer's disease. Understanding the differences between Early-MCI (EMCI) and Late-MCI (LMCI) is crucial to facilitate early diagnosis and future clinical interventions. This study employed free-water diffusion tensor imaging (FW-DTI) to explore the differences in white matter alterations between EMCI and LMCI.
View Article and Find Full Text PDFBackground: Predicting amyloid and tau status in nondemented older adults with AD pathologies using more affordable and accessible measures can facilitate clinical trials by reducing the screen failure rate. The goal of the present study was to develop tree-based ensemble models to predict PET-based amyloid and tau burden using non-invasive measures.
Method: Two datasets, amyloid (Aβ; n = 1062) and tau (n = 410), from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were used to predict the biomarker load in the subjects with normal cognition and mild cognitive impairment.
Biomarkers.
Alzheimers Dement
December 2024
University of California San Francisco (UCSF), San Francisco, CA, USA.
Background: As new anti-amyloid immunotherapies emerge for Alzheimer's disease (AD), it is clear that early diagnosis of AD pathology is crucial for treatment success. This can be challenging in atypical presentations of AD and, together with our reliance on CSF or PET scans, can, at times, lead to delayed diagnosis. Here, we further explore the possible role of plasma tau phosphorylated at threonine 217 (P-tau217) for the detection of primary AD or AD co-pathology when frontotemporal dementia spectrum disorders are the main clinical presentation.
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