Dataset Information

Mouse female hippocampus proteomics of Alzheimer Tg-SwDI Model

ABSTRACT: Cerebral Amyloid Angiopathy (CAA) is a significant comorbidity in almost all cases of Alzheimer’s disease (AD) and is unaddressed by current treatment regimens. We explored the Tg-SwDI mouse model which expresses human Amyloid Precursor Protein with the familial Swedish AD mutation as well as the vasculotropic Dutch and Iowa mutations leading to a phenotype of cognitive deficits with severe CAA. This is the first mapping of cerebral parenchymal proteomes of this model. In a cohort of presymptomatic mice both the cortex and hippocampus proteomes were mapped in male as well as female mice. In the four proteomes profound adaptations were identified, and previous findings of an early and severe pathology in Tg-SwDI female mice are reaffirmed on the molecular level. In addition, the effectiveness of two Carbonic Anhydrase Inhibitors (CAIs), Acetazolamide and Methazolamide, in preventing the observed molecular adaptations was evaluated. These repurposed drugs broadly prevented the proteome adaptations in the Tg-SwDI mice.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease 1

SUBMITTER: Johan Palmfeldt

LAB HEAD: Johan Palmfeldt

PROVIDER: PXD055083 | Pride | 2025-05-07

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	14-6-2022_EG-F-HC-Merge_PD2.5_PrecDet-SQ-Perc_Mut-Amyloid-DB.msf	Msf
	14-6-2022_EG-F-HC-Merge_PD2.5_PrecDet-SQ-Perc_Mut-Amyloid-DB_Proteins.txt	Txt
	TMT-Eug-fem-Hip-10.raw	Raw
	TMT-Eug-fem-Hip-2-excl.raw	Raw
	TMT-Eug-fem-Hip-2.raw	Raw

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Publications

Cerebral proteome adaptations to amyloid angiopathy are prevented by carbonic anhydrase inhibitors.

Carlsen Jasper J Fossati Silvia S Østergaard Leif L Gutiérrez-Jiménez Eugenio E Palmfeldt Johan J

Alzheimer's & dementia : the journal of the Alzheimer's Association 20250401 4

<h4>Background</h4>Cerebral amyloid angiopathy (CAA) is a hallmark of Alzheimer's disease (AD), linked to adverse effects of emerging AD treatments. We explored the molecular effects of CAA in mouse brain and evaluated how these could be prevented by two repurposed United States Food and Drug Administration (FDA) approved treatments.<h4>Methods</h4>Brain proteomics was performed on the Tg-SwDI genetic mouse model carrying disease causing mutations and developing AD characteristic cognitive defic ...[more]

PMID: 40285374

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