Harland, J. | Search bioRxiv

bioRxiv2021

Neuronal ROS-Induced Glial Lipid Droplet Formation is Altered by Loss of Alzheimers Disease-associated Genes

A growing list of Alzheimers disease (AD) genetic risk factors is being identified, but the contribution of these genetic mutations to disease remains largely unknown. Accumulating data support a role of lipid dysregulation and excessive ROS in the etiology of AD. Here, we identified cell-specific roles for eight AD risk-associated genes in ROS-induced glial lipid droplet (LD) formation. We demonstrate that ROS-induced glial LD formation requires two ABCA transporters (ABCA1 and ABCA7) in neurons, the APOE receptor (LRP1), endocytic genes (PICALM, CD2AP, and AP2A2) in glia, and retromer genes (VPS26 and VPS35) in both neurons and glia. Moreover, ROS strongly enhances A{beta}42-toxicity in flies and A{beta}42-plaque formation in mice. Finally, an ABCA1-activating peptide restores glial LD formation in the APOE4-associated loss of LD. This study places AD risk factors in a neuron-to-glia lipid transfer pathway with a critical role in protecting neurons from ROS-induced toxicity.

genetics↗

bioRxiv2020

The preservation of ancient DNA in archaeological fish bone

The field of ancient DNA is taxonomically dominated by studies focusing on mammals. This taxonomic bias limits our understanding of endogenous DNA preservation for vertebrate taxa with different bone physiology, such as teleost fish. In contrast to most mammalian bone, teleost bone is typically brittle, porous, lightweight and is characterized by a lack of bone remodeling during growth. Using high-throughput shotgun sequencing, we here investigate the preservation of DNA in a range of different bone elements from over 200 archaeological Atlantic cod (Gadus morhua) specimens from 38 sites in northern Europe, dating up to 8000 years before present. We observe that the majority of archaeological sites (79%) yield endogenous DNA, with 40% of sites providing samples that contain high levels (> 20%). Library preparation success and levels of endogenous DNA depend mainly on excavation site and pre-extraction laboratory treatment. The use of pre-extraction treatments lowers the rate of library success, although -- if successful -- the fraction of endogenous DNA can be improved by several orders of magnitude. This trade-off between library preparation success and levels of endogenous DNA allows for alternative extraction strategies depending on the requirements of down-stream analyses and research questions. Finally, we find that -- in contrast to mammalian bones -- different fish bone elements yield similar levels of endogenous DNA. Our results highlight the overall suitability of archaeological fish bone as a source for ancient DNA and provide novel evidence for a possible role of bone remodeling in the preservation of endogenous DNA across different classes of vertebrates.

evolutionary biology↗