11524 RESULTS
COMMENT In this comprehensive and detailed study, Wang et al. completed one of the most thorough analyses to reveal novel genetic underpinnings of PSP. They used whole-genome sequencing to analyze single-nucleotide variants, indels, and structural variants in nea
COMMENT Wang et al. performed whole-genome sequencing in more than 1,700 PSP patients, most of them confirmed by neuropathology. The authors confirm results from previous GWAS analyses and found other new relevant loci related to PSP risk. Among the multiple resu
COMMENT This GWA study shows that APOE2 is associated with higher risk and E4 with lower risk for PSP, a 4R tauopathy. That said, I don’t think we can say from this genetic analysis that it means that with PSP, E2 increases and E4 decreases tauopathy. Further bio
COMMENT For those of us studying APOE in the background of AD, this new preprint from Wang and Chang et al. certainly caught our attention. Here we have a situation where the “good guy” in AD (the APOE2 allele) is suddenly the “bad guy" in PSP. Although few
COMMENT This important paper represents a strong international cross-cohort collaboration to identify genetic associations of autopsy-confirmed PSP. There are some old culprits (MAPT, STX6, SLCO1A2, etc.), and some new suspects (TRIM24, TNXB, etc.), reflecting a
COMMENT In a commendable effort to prevent panic and shunning of AD patients, several expert commentators
COMMENT I would posit that the observations made can be explained by aging processes. If these patients received growth hormone in their childhood, one can assume that they are at risk for developmental abnormalities that result in abnormal brain aging. To claim
COMMENT One of the most pressing concerns for patients and their families is, "What will happen to me?" And right now we as clinicians are not very good at predicting how slowly or quickly individuals will progress in their disease. Patients and familie
COMMENT It is not true that only a "few people had enrolled in Envision." Over half the study population was enrolled, with the first subject enrolled about a year and a half ago, so it was perhaps on pace to complete enrollment this year. Adu's tr
COMMENT This paper reported very interesting findings that higher CSF GAP43 levels were associated with faster Aβ-related tau accumulation and spreading to connectivity-associated regions. This suggests a clear relation of the presynaptic protein to amyloid (A) a
COMMENT Immunization with fAβ42 (AN1792) results in a nearly complete absence of Aβ plaque deposits, both in mice that were vaccinated prior to the onset of amyloid deposition and in animals that were vaccinated after amyloid deposition was well underway. However
COMMENT Cancelling Aduhelm is an uncontroversial decision. Aducanemab was the vehicle on which FDA established its approval standards for amyloid antibodies: (1) plaque lowering buys accelerated approval, and (2) a touch of statistical significance on a composite
COMMENT This paper is impressive. It stands to become the pivotal reference work for the posterior cortical atrophy syndrome. It also reminds us that the mapping of syndrome to neuropathology is probabilistic rather than deterministic (Mesulam and Weintraub, 1992
COMMENT This work is by far the largest study of PCA to date. It solidifies evidence from many smaller studies that PCA is a distinct syndrome, usually causes young-onset dementia, mean age at onset about 60 years, and is almost always underpinned by Alzheimer’s
COMMENT As we explore the pathobiology of ApoE in AD and related dementias, there is an urgent need to understand the biochemical and biophysical properties of ApoE with the three main isoforms, ApoE2, ApoE3, and ApoE4 having differential effects on amyloids, cer
