11549 RESULTS
COMMENT This exciting pair of preprints explores the role of microglial lipid droplet accumulation in Alzheimer’s disease (AD) using complementary human and rodent model systems. Haney used AD brain tissue and human stem cell-derived microglia (iMG) and neurons,
COMMENT Wyss-Coray and colleagues have identified a key regulator of lipid droplet (LD) biogenesis, ASCL1, activated specifically in microglia and in APOE4 human AD brain, then followed by triacylglycerol (TAG) synthesis and lipid droplet (LD) accumulation. In vi
COMMENT These two studies make it abundantly clear that lipid droplets modulate microglial function in AD models. Over the past decade, the research community has rediscovered the importance of lipid droplet pathology in AD, and has made considerable strides in d
COMMENT Haney et al. and Prakash et al. focus on a little-studied attribute of the AD brain, i.e., the accumulation of lipids in glia, and their potential mechanistic role in neuronal cell death. As a rationale for their work, Haney et al. cite Alois Alzheimer’s
COMMENT I thoroughly enjoyed reading this elegant study. It nicely addresses the question of whether APOE4 exerts a gain-of-function role in the development of AD pathology and gives hope to the notion that therapeutically reducing APOE4 might be tolerated withou
COMMENT The previous Nature paper by the authors (Drieu et al., 2022) has demonstrated that parenchymal border macrophages (PBM) contribute to cerebrospinal fluid (CSF) flow, possibly by trimming the extracellular matrix, and that depletion of PBM by CLO leads to
COMMENT It seems like the amyloid-negative (A-) tau-medial temporal lobe-positive (TMTL+) phenotype overlaps very broadly with PART. PART has a different natural history than Alzheimer’s disease neuropathologic change (ADNC). In PART, the pathology stops at Braak
COMMENT In most earlier studies, CSF p-tau181 concentration has not been associated with tau tangle pathology as determined by tau PET or neuropathological examination, although one study from the Swedish BioFINDER study found weak correlations between CSF p-tau1
COMMENT The amyloid-negative (A-)/flortaucipir (FTP) medial temporal lobe (MTL)-positive (FTP-MTL+) group has not previously received attention, and the current report helped to fill that gap nicely. This is a well-done and clearly written piece that makes the po
COMMENT The editorial by Landau and Mormino very nicely summarizes the key “takeaways” of this study by Costoya-Sanchez et al. The study recapitulates some conclusions based on clinicopathological work published by my colleague, Joseph L. Price, and me many years
COMMENT I do have several concerns about the Quest direct-to-consumer test. Below are just some of them. First, there is no published data on the test’s performance or how the cutoffs were determined. Other blood tests that are currently clinically available, alb
COMMENT This is a very worrying development, and may harm the process of implementation of blood-based biomarkers. As the Dutch saying goes, “Trust arrives on foot, but leaves on horseback.” The lack of any data is a very serious problem. Even if the assay is sim
COMMENT That this test is being marketed directly to consumers tells us that people are worried about Alzheimer’s disease, and that they don’t always want to work through their regular doctor. This is complicated by the fact that many primary care doctors aren’t
COMMENT I am against offering a direct-to-consumer Aβ42/40 blood test for individuals to initiate themselves without oversight by an experienced AD provider, who has formally evaluated the person for AD and other potential neurological conditions in several stand
COMMENT I am generally against screening of healthy populations, unless rigorous science has shown that such screening approaches result in more good than harm. To do that, large-scale, population-based prospective studies are needed. Such studies should show tha
