Lorenza Magno on The Mutation You Want: It Protects the Brain, Extends Life

COMMENT The paper by van der Lee et al. is another in a series of genetic studies assessing the association between the rs72824905-G variant in the PLCG2 gene and neurodegenerative diseases (Conway et al., 2018; Kleineidam et al., 2018; Sims et al., 2017). The ...

Kariem Ezzat on When Host Proteins Coat Virus, Amyloid Fibrils Form

COMMENT In Figure 7, we report a significant net increase in the percentage of Aβ-positive areas by approximately 4 percent in the hippocampus and approximately 3 percent in the cortex. We respectfully point out that this is not the same thing as a fourfold ...

Nilufer Ertekin-Taner on The Mutation You Want: It Protects the Brain, Extends Life

COMMENT In 2017, using a whole-exome microarray and genotype imputation, a large three-stage case-control study of 85,133 participants identified an Alzheimer’s Disease (AD) protective coding variant in phospholipase C γ2 (PLCG2; Pro522Arg, rs72824905), a risk ...

Rita Guerreiro on The Mutation You Want: It Protects the Brain, Extends Life

COMMENT This study represents an independent replication of the association of PLCG2 rs72824905 with Alzheimer’s disease and suggests the possibility of an association with DLB, FTD, and longevity. Once an association with Alzheimer's disease is established ...

Todd E. Golde, David R. Borchelt on When Host Proteins Coat Virus, Amyloid Fibrils Form

COMMENT This is an intriguing study. The ex-vivo “test tube” studies are quite convincing that HSV and other virus particles can nucleate Aβ fibril formation.   However, we find the report in Figure 7 that inoculation of 3-month-old 5XFAD mice with HSV1 ...

Eric Larson on Is APOB a Risk Gene for Early Onset Alzheimer’s?

COMMENT It makes a lot of sense to look at early onset cases for potential genetic associations because early onset is clearly more strongly “genetic.” If we better understood how these variants work mechanistically, we might be able to design prevention or ...

Kariem Ezzat on When Host Proteins Coat Virus, Amyloid Fibrils Form

COMMENT In this work, we investigated whether viral corona interactions with host factors involve surface-assisted nucleation of amyloidogenic peptides. Similar to other phase-transition processes (such as crystallization, for example), the process of amyloid ...

Kim Green on Microglia Instigate ‘Chemofog’ by Squelching Myelination

COMMENT This paper, combined with the Monje lab’s recent Cell paper (Gibson et al., 2018), elegantly highlights the complexity of cellular interactions in toxicity/disease states, and place microglia as the major effector cell type that has broad effects on ...

Tjakko Van Ham on Microglia Instigate ‘Chemofog’ by Squelching Myelination

COMMENT This is a very interesting paper providing further evidence, in a mouse model, for how chemotherapy—specifically methotrexate/MTX—could affect cognition, and how this involves multiple glial cell types, eventually leading to defective adaptive myelination ...

Marcia Ratner on Brainstem GABAergic Inputs to Hippocampus Control Memory Formation

COMMENT Arousal depends on the activation of ascending neural pathways originating in the brainstem (pons and medulla). The nucleus incertus (NI) is a conserved area within the pontine periventricular region that consists of ascending GABAergic projection neurons ...

Yadong Huang on Brainstem GABAergic Inputs to Hippocampus Control Memory Formation

COMMENT This is a beautiful and exciting study showing conclusively that brainstem nucleus incertus (NI) GABAergic neurons control hippocampal-dependent contextual memory formation by inhibiting hippocampal somatostatin (SOM) interneurons in the stratum orients, ...

Heidi Jacobs on Brainstem GABAergic Inputs to Hippocampus Control Memory Formation

COMMENT This study adds more evidence to the fascinating role of evolutionarily ancient brainstem nuclei, such as the locus coeruleus and the nucleus incertus in higher-order cognitive functions. The nucleus incertus consists of mostly GABAergic projection ...

Andrea Tenner on Are Disease Mutations Lurking Within ‘Dark Regions’ of the Genome?

COMMENT As the news article notes, this manuscript does an excellent job of pointing out the caveats of standard short-read sequencing technologies, the basis for the “dark” and “camouflaged” regions, and how these deficiencies impact our effort to map out the ...

Michele Vendruscolo on When Host Proteins Coat Virus, Amyloid Fibrils Form

COMMENT This study is important because it provides a mechanism of action that rationalizes previous epidemiological observations of a correlation between herpes and Alzheimer's disease. Alzheimer's is characterized by the deposition of the Aβ peptide ...

Hugo Lövheim on When Host Proteins Coat Virus, Amyloid Fibrils Form

COMMENT This paper provides further detail on the interaction between herpes simplex type 1 and Aβ. The results are in line with those presented by Robert Moir's group last year (Eimer et al., 2018). They confirm that the presence of viral particles ...