Detecting the effect of genetic diversity on brain composition in an Alzheimer's disease mouse model.
Brianna GurdonSharon C YatesGergely CsucsNicolaas E GroeneboomNiran HadadMaria TelpoukhovskaiaAndrew OuelletteTionna OuelletteKristen M S O'ConnellSurjeet SinghTom MurdyErin MerchantIngvild BjerkeHeidi KlevenUlrike SchlegelTrygve B LeergaardMaja A PuchadesJan G BjaalieCatherine C KaczorowskiPublished in: bioRxiv : the preprint server for biology (2023)
Alzheimer's disease (AD) is characterized by neurodegeneration, pathology accumulation, and progressive cognitive decline. There is significant variation in age at onset and severity of symptoms highlighting the importance of genetic diversity in the study of AD. To address this, we analyzed cell and pathology composition of 6- and 14-month-old AD-BXD mouse brains using the semi-automated workflow (QUINT); which we expanded to allow for nonlinear refinement of brain atlas-registration, and quality control assessment of atlas-registration and brain section integrity. Near global age-related increases in microglia, astrocyte, and amyloid-beta accumulation were measured, while regional variation in neuron load existed among strains. Furthermore, hippocampal immunohistochemistry analyses were combined with bulk RNA- sequencing results to demonstrate the relationship between cell composition and gene expression. Overall, the additional functionality of the QUINT workflow delivers a highly effective method for registering and quantifying cell and pathology changes in diverse disease models.
Keyphrases
- single cell
- cognitive decline
- genetic diversity
- gene expression
- cell therapy
- mouse model
- quality control
- white matter
- mild cognitive impairment
- cerebral ischemia
- escherichia coli
- high throughput
- machine learning
- multiple sclerosis
- inflammatory response
- dna methylation
- deep learning
- stem cells
- spinal cord
- electronic health record
- physical activity
- subarachnoid hemorrhage
- sleep quality