Vertebrobasilar arterial occlusions in children

Three children with angiographically confirmed, sudden thrombosis involving the vertebro basilar arterial system are presented. Ten previously reported cases are reviewed with particular regard to possible etiologies. Vertebral artery trauma at the atlantoaxial level is suspected as one important cause. Les auteurs rapportent trois cas d'enfants présentant une trombose soudaine du système artériel vertébrobasilaire, confirmée angiographiquement. Ils revoient dix cas antérieurs, en particulier du point de vue éthiologique. Le traumatisme de l'artère vertébrale au niveau de la charnière cervico-occipitale semble être l'une des causes principale. 3 Kinder mit einer angiographisch nachgewiesenen plötzlich aufgetretenen thrombose des vertebro-basilären Systems werden geschildert, gleichzeitig wird ein Überblick über weitere 10 vorher veröffentlichte Fälle gegeben. Diskussion der möglichen Ätiologie. Es wird darauf verwiesen, daß ein Trauma der A. vertebralis in Höhe des atlanto-axialen Gelenkes eine wichtige Ursache sein kann.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46670/1/234_2004_Article_BF00341593.pd

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues