11526 RESULTS
COMMENT In Alzheimer’s disease research, a key lingering question regards how, precisely, remote neocortical Aβ influences medial temporal tau neurofibrillary pathology. This question can and should be examined at multiple levels to provide a comprehensive mechan
COMMENT Activity and communication across large-scale brain networks, spanning multiple regions, are known to be disrupted in AD (Harris et al., 2020). However, it is not clear whether these changes are a cause of disease progression and phenotype or merely an ex
COMMENT This exciting technology brings the depth and established workflows of single-cell analyses into spatial genomics. With the understanding that spatial context is key to understanding biology, genomics tools have begun mapping molecules in situ. Alas, thes
COMMENT This study provides nice insights into aging at the molecular level, gained through proteomics applications. That the investigators were able to generate such a powerful dataset, and analyze the mass of data, shows how far proteomics technology and machin
COMMENT This new study provides one of the most comprehensive approaches to date on how aging intersects with many disorders for which it acts as a major risk factor. One major strength is Oh et al.'s leveraging of a large-scale protein quantification approa
COMMENT The finding for filaments composed of TAF-15 is interesting but not entirely unexpected. We initially introduced the terminology “FTLD-FUS” for these subtypes of tau/TDP-negative FTLD because FUS was the first protein component of the inclusions identifie
COMMENT A unifying theme for neurodegenerative disorders is the abnormal accumulation of protein aggregates in the central nervous systems of affected individuals. Over the last ~20 years, the isolation of the proteinaceous building blocks of these pathological d
COMMENT Protective missense variants in APOE—or those that change an amino acid in the protein sequence of APOE—are very rare. Nonetheless, they are incredibly important because understanding how they nearly abrogate an increased risk of AD may pave the way to ne
COMMENT In 2019, a rare variant on an APOE3 background (APOE3-R136S), Christchurch mutation, when present in the homozygous state, was found to be associated with a marked delay in cognitive decline in an individual with the PSEN1-E280A mutation that causes autos
COMMENT As demonstrated by our original APOE Christchurch publication (Arboleda-Velasquez et al., 2019), case reports can be exceptionally sensitive in uncovering new mechanisms, offering unique insights into biology, pathophysiology, and, in this instance, resis
COMMENT In 2019, Arboleda-Velasquez et al. reported the remarkable case of a woman who harbored the highly penetrant PSEN1-E280A Alzheimer’s mutation, but was spared the disease for 28 years beyond the mean age of onset that occurred in the late 40s of the other
COMMENT In a commendable effort, Oh and colleagues identified a set of organ-specific proteins that were then used to compute organ-specific age and age gaps. By taking a set of proteins that were specifically expressed in brain tissue and mapped onto cognitive f
COMMENT This is wonderful work. It truly lays out the basis for translation to the clinic of plasma proteomic analysis, a powerful method that so far has been used almost exclusively for research purposes (some application in oncology excluded). The authors measu
COMMENT readout, incidence of MCI and dementia. I am also endorsing the thoughtful comment by Dr. Harrison.
COMMENT This is a very elegant, timely, and superb study by the Iadecola lab. It was not known by what mechanisms hypertension causes cognitive impairment. Here, the authors used a sophisticated, salt-sensitive model to decipher the underlying mechanistical steps
