Amyloid-associated hyperconnectivity drives tau spread across connected brain regions in Alzheimer's disease.

In Alzheimer's disease (AD), amyloid-β (Aβ) triggers the aggregation and spreading of tau pathology, which drives neurodegeneration and cognitive decline. However, the pathophysiological link between Aβ and tau remains unclear, which hinders therapeutic efforts to attenuate Aβ-related tau accumulation. Aβ has been found to trigger neuronal hyperactivity and hyperconnectivity, and preclinical research has shown that tau spreads across connected neurons in an activity-dependent manner.

Locus coeruleus signal intensity and emotion regulation in agitation in Alzheimer's disease.

Hyperphosphorylated tau accumulation is seen in the noradrenergic locus coeruleus from the earliest stages of Alzheimer's disease onwards and has been associated with symptoms of agitation. It is hypothesized that compensatory locus coeruleus-noradrenaline system overactivity and impaired emotion regulation could underlie agitation propensity, but to our knowledge this has not previously been investigated. A better understanding of the neurobiological underpinnings of agitation would help the development of targeted prevention and treatment strategies.

Carboxyl ester lipase hybrid 1 (CEL-HYB1) haplotypes confer varying risk for chronic pancreatitis.

The CEL-HYB1 hybrid allele of the carboxyl ester lipase (CEL) gene and its pseudogene (CELP) has been associated with chronic pancreatitis (CP). Recent work indicated that amino acid positions 488 and 548 in CEL-HYB1 determined pathogenicity. Haplotype Thr488-Ile548 was associated with CP while haplotypes Thr488-Thr548 and Ile488-Thr548 were benign.

Artificial intelligence-based rapid brain volumetry substantially improves differential diagnosis in dementia.

Introduction: This study evaluates the clinical value of a deep learning-based artificial intelligence (AI) system that performs rapid brain volumetry with automatic lobe segmentation and age- and sex-adjusted percentile comparisons.

Methods: Fifty-five patients-17 with Alzheimer's disease (AD), 18 with frontotemporal dementia (FTD), and 20 healthy controls-underwent cranial magnetic resonance imaging scans. Two board-certified neuroradiologists (BCNR), two board-certified radiologists (BCR), and three radiology residents (RR) assessed the scans twice: first without AI support and then with AI assistance.

Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects.

Background: Quantification of Amyloid beta (Aβ) oligomers in plasma enables early diagnosis of Alzheimer's Disease (AD) and improves our understanding of underlying pathologies. However, quantification necessitates an extremely sensitive and selective technology because of very low Aβ oligomer concentrations and possible interference from matrix components.

Methods: In this report, we developed and validated a surface-based fluorescence distribution analysis (sFIDA) assay for quantification of Aβ oligomers in plasma.