Mark Tuszynski on Toward an AD CRISPR Therapy: Tweaking APP Terminus Cuts Plaque

COMMENT Admitting a conflict of interest in commenting on this research (Subhojit's office is two

Justyna Dobrowolska Zakaria on Remember Amyloid-eta? A Decade Later, News on a Physiological Function

COMMENT This report provides exciting new insights into the potential physiological role of a proteolytic cleavage fragment of amyloid precursor protein (APP), known as Aη (AETA), which was first discovered by the authors about a decade ago (Willem et al., 2015).

Sergio Escamilla, Immaculada Cuchillo Ibañez, Javier Saez-Valero on Remember Amyloid-eta? A Decade Later, News on a Physiological Function

COMMENT Several secretases are involved in the proteolytic processing of the amyloid precursor protein (APP) and, as a result, different proteolytic fragments are generated. How APP fragments interact and influence APP proteolytic processing merit profound resear

Florian Merkle on Blood May Foretell Parkinson’s Up to Seven Years Prior

COMMENT The best treatment for Parkinson’s Disease (PD) would be to prevent the loss of existing dopaminergic neurons, but it is challenging to identify individuals who would benefit from such an intervention. This study from Hällqvist and colleagues is an import

George Kannarkat on Blood May Foretell Parkinson’s Up to Seven Years Prior

COMMENT This biomarker study establishes a novel, mass-spectrometry-based paradigm to identify, in an unbiased manner, biomarker proteins in blood that differentiate healthy individuals from those with Parkinson’s disease. Within this study, a panel of eight prot

Qingyun (Tristan) Li on T Cells in the Brain Goad Microglia to Muddle Myelin

COMMENT This elegant paper from Mikael Simons’ lab focuses on a less-studied pathological feature in Alzheimer’s disease (AD)—myelin damage—and it provides mechanistic insights into the interplay between the innate and adaptive immune systems that mediate this pr

Christoph Gericke on T Cells in the Brain Goad Microglia to Muddle Myelin

COMMENT This study by Kedia et al. adds to the growing evidence that the CD8+ T cell compartment is associated with, and possibly even actively involved in, AD pathology. The phenomenon of elevated numbers of CD8+ T cells in postmortem AD brain tissue has been kn

David Gate on T Cells in the Brain Goad Microglia to Muddle Myelin

COMMENT This is yet another impressive study on the impact of brain-penetrant T cells on white matter. As a follow-up to their noteworthy 2022 publication, in which they demonstrated that T cells accumulate in white matter with aging (Kaya et al., 2022), the Simo

Alma Mohebiany, Renzo Mancuso on T Cells in the Brain Goad Microglia to Muddle Myelin

COMMENT The study from Kedia et al. examines the role of brain-infiltrating CD8+ T cells in promoting white-matter damage. Using two models of Alzheimer’s disease (5XFAD and AppNL-G-F), removing CD8+ T cells reduced myelin abnormalities, and had positive effects

Xiaoying Chen, David Holtzman on T Cells in the Brain Goad Microglia to Muddle Myelin

COMMENT There is strong evidence that both the innate and adaptive immune responses contribute to different aspects of Alzheimer’s disease (AD) development and progression. The role of immune responses and their interaction with myelinating oligodendrocytes remai

Mehdi Jorfi, Rudy Tanzi on T Cells in the Brain Goad Microglia to Muddle Myelin

COMMENT This work provides compelling evidence that CD8+ T cells and microglia interactions are pivotal in the myelin pathology observed in Alzheimer’s disease (AD). Using the 5xFAD mouse model, the authors demonstrated that CD8+ T cells trigger microglial activa

Perminder Sachdev on Estimates of Young-Onset Dementia Prevalence Just Doubled

COMMENT The upper age limit of YOD remains disputed. Perhaps one should try to ascertain an empirical cut-off rather than using 65 years as an administrative one. A number of factors should go into this: 1. If one looks at the inflection point for prevalence esti

Gesine Saher on Microglial Transplants Reverse Age-Related Pathology in Mice

COMMENT These two exciting papers by Munro et al. and Chadarevian et al. significantly advance our understanding of microglial function in maintaining brain integrity, demonstrating that these remarkable cells play a crucial role in preventing more pathological a

Sabina Tahirovic on Microglial Transplants Reverse Age-Related Pathology in Mice

COMMENT These two excellent studies explore FIRE mice to model rare autosomal-dominant leukodystrophy (ALSP). FIRE mice carry a homozygous loss of the key microglial-regulating gene CSF1R, and thus lack microglia. Of note, most ALSP patients carry a heterozygous

Nóra Baligács, Bart De Strooper on Microglial Transplants Reverse Age-Related Pathology in Mice

COMMENT These two fascinating publications build on the landmark paper that demonstrated the generation of a mouse completely devoid of microglia by simply removing a specific enhancer in the promoter of the CSFR1 gene (Rojo et al., 2019). The surprise at that ti