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Co-evolution of atypical BRAF and KRAS mutations in colorectal tumorigenesis.
Mol Cancer Res
January 2024
University of Oxford, Oxford, United Kingdom.
BRAF mutations in colorectal cancer (CRC) comprise three functional classes: Class 1 (V600E) with strong constitutive activation, Class 2 with pathogenic kinase activity lower than Class 1, and Class 3 which paradoxically lacks kinase activity. Non-Class 1 mutations associate with better prognosis, microsatellite stability, distal tumour location and better anti-EGFR response. Analysis of 13 CRC cohorts (n=6,605 tumours) compared Class 1 (n=709, 10.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Amsterdam UMC, location VUmc, Department of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam, Netherlands.
Background: Recent studies highlight distinct patterns of cortical atrophy between amnestic (typical) and non-amnestic (atypical, with subtypes: behavioural, dysexecutive, logopenic and visuospatial) clinical phenotypes of Alzheimer's disease (AD). The current study aimed to assess regional MRI patterns of cortical atrophy across AD phenotypes, and their association with amyloid-beta (Aβ), phosphorylated tau (pTau), axonal degeneration (NfL) and microvascular deterioration (COLIV).
Method: Postmortem In-situ 3DT1 3T-MRI data was collected for 33 AD (17 typical, 16 atypical) and 16 control brain donors.
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
Department of Pathology, University of Sao Paulo Medical School, São Paulo, São Paulo, Brazil.
Background: Alzheimer's disease (AD) features stereotypical spread of hyperphosphorylated tau (p-tau) and beta-amyloid. Although other pathological tau posttranslational modifications (PTMs) have been described in AD, a prevalent disease model preconizes that other tau PTMs always coincide with p-tau, making the latter an excellent marker of pathological tau burden. We showed in experimental studies that truncated tau (tr-tau), a pathological tau PTM generated via cleavage by active caspases, is as common as p-tau in neurons at late AD stages; however, only about 40% of tr-tau positive neurons also show p-tau positivity.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Yale School of Medicine, New Haven, CT, USA.
Background: Affective cognition and emotion processing is impaired in amnestic Alzheimer's disease (AD), although less is known about atypical (AT) variants such as logopenic variant primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA). The affective blindsight pathway bypasses V1 via the superior colliculus-pulvinar route to activate the amygdala in cases of occipital lesioning and may explain maintenance of emotion identification and visual information processing in non-amnestic AD despite atrophy in visuospatial regions. We sought to characterize functional connectivity from key regions along the affective blindsight pathway in a clinically heterogeneous AD cohort.
View Article and Find Full Text PDFClinical Manifestations.
Alzheimers Dement
December 2024
Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, Netherlands.
Background: Young onset dementia (YOD) is characterized by an atypical clinical manifestation, and it is unclear to what extent impairments in everyday functioning are part of this manifestation. This study aims to describe the prevalence and differences of difficulties in instrumental activities of daily living (IADL) in YOD.
Methods: In this cross-sectional study, 394 subjects with sporadic YOD (onset<65 years,mean(M)age 58.
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