Nascent Aβ42 Fibrillization in Synaptic Endosomes Precedes Plaque Formation in a Mouse Model of Alzheimer's-like β-Amyloidosis.

Accumulation of amyloid-β peptide (Aβ) aggregates in synapses may contribute to the profound synaptic loss characteristic of Alzheimer's disease (AD). The origin of synaptic Aβ aggregates remains elusive, but loss of endosomal proteostasis may trigger their formation. In this study, we identified the synaptic compartments where Aβ accumulates, and performed a longitudinal analysis of synaptosomes isolated from brains of TgCRND8 APP transgenic mice of either sex.

The effect of increased collect pump rate on collection efficiency in hematopoietic progenitor cell collection by apheresis in allogeneic adult donors-A single center analysis.

Background: Optimizing CD34 recovery while minimizing harm to hematopoietic progenitor cell donors by apheresis (HPC(A) donors) is critical to the success of allogeneic hematopoietic cell transplantation. We examined the efficacy and safety of starting allogeneic HPC(A) donors at a collect pump rate (CPR) of 2 mL/min on the Spectra Optia regardless of the inlet flow rate and/or pre-apheresis white blood cell (WBC) count (high CPR group).

Study Design And Methods: A single-center retrospective study was performed on allogeneic adult donors from 10/2020 to 12/2022.

Brain Targeted AAV1-GALC Gene Therapy Reduces Psychosine and Extends Lifespan in a Mouse Model of Krabbe Disease.

Krabbe disease (KD) is a progressive and devasting neurological disorder that leads to the toxic accumulation of psychosine in the white matter of the central nervous system (CNS). The condition is inherited via biallelic, loss-of-function mutations in the galactosylceramidase () gene. To rescue gene function in the CNS of the twitcher mouse model of KD, an adeno-associated virus serotype 1 vector expressing murine under control of a chicken β-actin promoter (AAV1-GALC) was administered to newborn mice by unilateral intracerebroventricular injection.

Spinal fluid IgG antibodies from patients with demyelinating diseases bind multiple sclerosis-associated bacteria.

A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of patients with demyelinating diseases (DD). The anti-microbial ELISA assays follow on prior human brain tissue RNA sequencing studies that established multiple sclerosis (MS) microbial candidates. Lysates included in the ELISA panel were derived from Akkermansia muciniphila, Atopobium vaginae, Bacteroides fragilis, Lactobacillus paracasei, Odoribacter splanchnicus, Pseudomonas aeruginosa, Cutibacterium (Propionibacterium) acnes, Fusobacterium necrophorum, Porphyromonas gingivalis, and Streptococcus mutans.

Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-β oligomerizes.

Pleiotropic roles are proposed for brain extracellular vesicles (EVs) in the development of Alzheimer's disease (AD). Our previous studies have suggested a beneficial role for EVs in AD, where the endosomal system in vulnerable neurons is compromised, contributing to the removal of accumulated material from neurons. However, the involvement of EVs in propagating AD amyloidosis throughout the brain has been considered because the amyloid-β precursor protein (APP), APP metabolites, and key APP cleaving enzymes were identified in association with EVs.