Production of amyloid ß in hereditary cerebral hemorrhage with amyloidosis-Dutch type

Amyloid ß cerebral amyloid angiopathy (Aß CAA), that is, the deposition of Aß
amyloid in the walls of cerebral blood vessels, is associated with cerebral
hemorrhage and dementia. Aß CAA is the pathologic hallmark of the rare disease
hereditary cerebral amyloid angiopathy-Dutch type (HCHWA-D). HCHWA-D is caused
by a mutation in the gene encoding the Aß precursor protein (AßPP). Aß CAA can
also occur as a sporadic entity and it is a frequent feature of the pathology
of Alzheimer's disease. The pathogenesis of Aß CAA is unknown and the
mechanisms by which CAA may lead to cerebral hemorrhage and dementia are not
clear. Being a monogenic disorder HCHWA-D is an excellent model for the study
of these issues. Recent studies of the brains of HCHWA-D patients and
transgenic mice suggest that relative changes in the production of the diverse
Aß species from AßPP could play a role in the pathogenesis of Aß CAA.

The objective of the study is to determine whether the HCHWA-D gene mutation
affects the proteolysis of AßPP with regard to the ratio of the diverse Aß
species produced from AßPP.

Observational study with invasive measurements (skin biopsy).

A 4mm skin biopsy will be performed once. The procedure will take 10 minutes.
The risks include scarring and a small chance of infection of the wound
(1.6-3%).