11526 RESULTS
COMMENT Tau double phosphorylation at residues 202 and 205 is one of the hallmarks of brain tau aggregates and has been used over the last decades for neuropathological studies on tau aggregation using the AT8 antibody. In cerebrospinal fluid, multiple phosphoryl
COMMENT This new report by Franzmeier et al. is a beautiful continuation of investigations into the important interplay between Aβ, tau, and neuronal hyperexcitability in the context of Alzheimer's disease. There have long been reports of how the presence of
COMMENT In this paper, the authors conducted an interesting secondary analysis of CSF and longitudinal tau PET data from ADNI. CSF levels of GAP-43, a presynaptic protein important in neurodevelopment and in axonal regeneration, are increased in MCI and AD, and h
COMMENT The take-home message from this research article is that in AD, synaptic changes, manifested by increased levels of the presynaptic protein GAP-43, are closely associated with the accelerated spread of tau pathology. The study found that higher levels of
COMMENT The recent article by Franzmeier et al. demonstrated, with a series of very elegant analyses, that the synaptic biomarker GAP-43 associates with the spreading and accumulation of Aβ-related tau pathology. The study somewhat challenges the perhaps more “tr
COMMENT Nobuhisa Iwata, a former member of my laboratory and currently professor of Nagasaki University, quantified plasma Aβ40 and 42 in wild-type and neprilysin knockout mice. Aβ40 and 42 were 1.6 and 1.7 times higher in the knockout mice, respectively, and the
COMMENT The term neurovascular coupling was coined in 2001 to indicate the interaction between brain activity and brain blood supply. While approximately a century ago it was believed that the vessels supplying blood to the brain and the brain cells function inde
COMMENT This study identified risk factors for young-onset dementia, including: lower formal education, lower socioeconomic status, carrying two apolipoprotein e4 alleles, no alcohol use, alcohol use disorder, social isolation, vitamin D deficiency, high C-reacti
COMMENT This publication carefully identifies and validates downstream effects of knockdown or pharmacologic inhibition of INPP5D in microglia induced from human iPSCs (iMGs). It follows on the heels of multiple studies examining effects in constitutive and condi
COMMENT Chou and colleagues have added important insights into the role of INPP5D in Alzheimer's disease. Their study shows that in AD brains, despite increased INPP5D expression, the predominant protein is in a truncated, potentially dysfunctional form. Thi
COMMENT This study utilizes task fMRI to look at repetition suppression in 42 older adults, of whom 21 had evidence of abnormal amyloid pathology. Task-evoked paradigms are a powerful tool to understand complex cognitive constructs, and they are underutilized in
COMMENT This study identifies a new player in the regulation of neuroinflammation in AD. In a GWAS, mutations of the myeloid-specific gene INPP5D have been found to be associated with the risk of developing late-onset AD. INPP5D encodes the phosphatase SHIP1, whi
COMMENT This study provides new insights into the role of INPP5D in AD pathology and its potential mechanism of action within the axis of microglial NLRP3 inflammasome activation. The study used multiomics approaches to profile transcriptomic and proteomic landsc
COMMENT Giorgio and colleagues investigate changes in neuronal activity as a potential link between Aβ and tau accumulation. The study appears motivated by previous work showing that Aβ can induce a shift of neuronal activity toward hyperexcitability (e.g., via a
COMMENT Georgio et. al. provide support for a model where Aβ in the DMN drives hyperexcitability leading to hyperexcitability in the medial temporal lobe MTL and accumulation of tau. The study uses fMRI BOLD signal while subjects perform a mnemonic discrimination
