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Although transcranial sonography (TCS) assessing hyperechogenic substantia nigra (SN+) as biomarker for Parkinsońs disease (PD) has been introduced elsewhere, the clinical relevance and accuracy in a Swedish population is still unknown.This retrospective single-center study included 74 patients with predominantly early-stage parkinsonism at first visit who had been examined by TCS from 2013 to 2017 to determine the SN+ biomarker status in relation to PD, atypical parkinsonian disorders (APS), essential tremor (ET) and vascular/secondary/ unspecified parkinsonism, with the aim of long-term follow-up to confirm the clinical diagnosis. The cut-off value for SN+ was regarded as the 90 % percentile of SN echogenicity in a local healthy cohort (here, 0.23 cm2).In 2024, the mean follow-up time was 95 months. [...]

Autoimmune encephalitis (AIE) with anti-leucine-rich glioma-inactivated 1 (LGI1) antibodies typically manifests with subacute cognitive deficits, seizures, and psychiatric symptoms, mostly in older adults. Immunotherapy (IT) leads to the cessation of seizures in most patients, yet some develop AIE-associated epilepsy (AEAE) and persistent cognitive deficits. [...]

BackgroundInflammation is recognized as a key hallmark of Alzheimer’s disease (AD), alongside amyloid beta (Aβ) accumulation and tau pathology. Recent evidence suggests that neuroinflammatory markers in cerebrospinal fluid (CSF) are associated with progressive neurodegeneration and regional brain atrophy. [...]

Background:Mnemonic discrimination (MD), the ability to distinguish between similar but distinct memories, relies heavily on the integrity of key medial temporal lobe (MTL) regions. Aging is associated with declines in MD, but evidence suggests that cognitive training may help mitigate this decline. [...]

BackgroundAmyloid related imaging abnormalities (ARIA) are a common side effect of monoclonal anti-amyloid antibodies and limit the benefit risk ratio. Here we investigate the safety and efficacy of the anti-oligomeric all-D-peptide PRI-002 in early AD. [...]

Background:The apolipoprotein E (APOE) ε4 allele remains the strongest genetic risk factor for late-onset Alzheimer’s disease (AD), yet the marked variability in its pathogenicity suggests underlying genetic complexity. Historically, efforts to resolve the intragenic architecture of APOE have been hampered by the limitations of conventional genotyping and short-read sequencing, as well as the presence of homoplasy in common intragenic markers—misleading similarities arising from convergent variants.Objective:We leveraged Oxford Nanopore Technology (ONT) to phase intragenic APOE variants, resolve homoplasy, and examine the impact of phased haplotypes on cerebrospinal fluid (CSF) APOE protein levels and AD progression.Methods:Using long-read sequencing in a Spanish memory clinic cohort (n = 1,267), we reconstructed full-length 4 kb APOE haplotypes, identifying 59 unique configurations grouped into five major haplogroups. [...]

Background:Improved memory for negative events is supported by the locus coeruleus-noradrenergic (LC-NA) system. As the LC is one of the first structures exhibiting tau pathologies in AD, in vivo markers for structural and functional changes in the LC are required. [...]

Background:Advances in disease-modifying treatments and blood-based biomarkers for Alzheimer's disease (AD) have increased the importance of early diagnosis and dementia risk estimation before symptom onset. Autonomous decisions about AD risk estimation are complex and should align with individual needs and preferences. [...]

Background:The molecular basis for accelerated cognitive decline seen in Alzheimer's Disease (AD) cases presenting with cortical alpha-Synuclein co-pathology is not well understood. Mouse experiments have shown adverse interactions between tau (encoded by MAPT) and alpha-Synuclein (encoded by SNCA), but how this finding translates to humans from a genome-centered point of view remains unknown.Method:Whole genome sequencing was performed on 137 neuropathologically defined AD cases, 36 of which presented with neocortical alpha-Synuclein co-pathology (Braak stage 6). [...]

Background:Tau accumulation drives neurodegeneration and cognitive decline in Alzheimer's Disease (AD) and preclinical research suggests that tau spreads transsynaptically across connected neurons. We translated tau spreading models to human neuroimaging data, showing that tau pathology spreads from circumscribed epicenters to connected regions in AD, following the architecture of functional brain networks. [...]