Carbonic anhydrase inhibitors prevent presymptomatic capillary flow disturbances in a model of cerebral amyloidosis.

ABSTRACT

To enhance early diagnosis and treatment of Alzheimer·s disease (AD), understanding the pathological changes before symptoms arise is crucial. The continuum model of AD suggest that Aß beta (Aß) accumulation precedes symptoms by at least 15 years, with vascular changes detectable around this time. Disturbances in capillary flow dynamics have been linked to reduced oxygen delivery to brain tissue, but evidence in presymptomatic AD remains elusive. We examined capillary flow dynamics in presymptomatic Tg-SwDI mice and the capacity of carbonic anhydrase inhibitors (CAIs) to prevent capillary flow disturbances. Our study revealed capillary flow disturbances associated with alterations in capillary morphology, adhesion molecule expression, and Aß load in cognitively normal 9-10-month-old Tg-SwDI mice. Treated mice showed ameliorated capillary flow disturbances, enhanced oxygen availability, and reduced Aß load. These findings underscore the importance of capillary flow disturbances in presymptomatic AD and highlight CAIs· potential for preserving vascular integrity in early AD.