Mutations: APP E693Q (Dutch)
Modification: APP: Transgenic
Disease Relevance: Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type, Cerebral Amyloid Angiopathy, Alzheimer's Disease
Strain Name: C57BL/6J-Tg(Thy1-APPDutch)
Genetic Background: C57BL/6J
Availability: Available through Mathias Jucker.
This transgenic mouse line bears a mutation that was determined to cause hereditary cerebral hemorrhage with amyloidosis-Dutch type, a rare autosomal dominant disorder characterized by cerebral amyloid angiopathy (CAA), strokes, and dementia. APPDutch mice have an increased Aβ40/Aβ42 ratio, but parenchymal amyloid plaques are not observed. Instead, mice develop extensive vascular Aβ deposition starting at 22 to 24 months of age, and appearing first in leptomeningeal vessels followed by cortical vessels. This leads to smooth muscle cell degeneration, hemorrhages, and neuroinflammation. The mice develop robust microgliosis immediately adjacent to amyloid-laden vessels, and widespread activation of astrocytes in neocortical regions affected by CAA. Female mice have earlier onset of amyloid deposition (Herzig et al., 2004).
Transgenic mice with human APP751 bearing the E693Q mutation under the murine Thy1 promoter.
When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.
- Neuronal Loss
- Synaptic Loss
- Changes in LTP/LTD
- Cognitive Impairment
No plaques are observed, but CAA develops at 22-24 months.
Microgliosis develops after the onset of CAA pathology and is prominent in areas adjacent to amyloid-laden vessels. There is also widespread activation of astrocytes in neocortical regions affected by CAA. These changes have been reported at 29 months of age, although the actual onset of gliosis may occur earlier than has been examined.
Changes in LTP/LTD
- Herzig MC, Winkler DT, Burgermeister P, Pfeifer M, Kohler E, Schmidt SD, Danner S, Abramowski D, Stürchler-Pierrat C, Bürki K, van Duinen SG, Maat-Schieman ML, Staufenbiel M, Mathews PM, Jucker M. Abeta is targeted to the vasculature in a mouse model of hereditary cerebral hemorrhage with amyloidosis. Nat Neurosci. 2004 Sep;7(9):954-60. PubMed.
No Available Further Reading