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P4‐218: CAA IN MUTANT AD MICE: A COMPARATIVE STUDY TO HUMAN AD CASES
Author(s) -
Havas Daniel,
Temmel Magdalena,
Attems Johannes,
Hutter Heinz,
HutterPaier Birgit
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.1736
Subject(s) - pathology , cerebral amyloid angiopathy , angiogenesis , amyloid (mycology) , vascular smooth muscle , biology , medicine , disease , endocrinology , dementia , smooth muscle
Changes of gross vascular morphology were reported for different mouse models of Alzheimer’s disease (AD) and for human AD cases. Those changes comprise cerebral amyloid angiopathy (CAA) but also increased IR area of vascular markers such as Collagen IV. The latter was interpreted as vascular sprouting and/or increase of vascular diameter. However, this interpretation is critical within two respects: A) Sprouting or diameter alteration are two totally different mechanisms to increase blood flow as a reaction to lacking nourishment as found in AD. Thus it is important to figure out, which one exactly is responsible for increased vascular marker signal. B) The translationability of findings in mouse models to human cases has to be investigated. Uniform systematic random sets of brain sections deriving a) from AD model APP SL transgenic (Tg) mice at three ages (months 6; 9 ;12) and b) from human AD cases* of three different Braak stages (Braak stages I/II; III/IV; V/VI) were immunohistochemically labeled for detection of amyloid (clone 6E10) and vessels (SMA, Collagen IV), imaged and quantitatively evaluated in terms of mean vascular diameter and percentage of amyloid related to vascular cross section area using image analysis software (Axio.Imager Z1 microscope, ImageProPlus). Sections of non-transgenic littermate mice (nTg) and age-matched non AD human subjects served as controls. In mice mean arterial cross sectional size was evaluated by manual delineation of smooth muscle actin (SMA, specific to arteries in the brain) labeling of 11 defined arteries in the cerebral cortex at three different lateral levels of the brain. Data are meta-data and derive from Tg and nTg vehicle controls of different studies. Since SMA did not label on human sections (formalin over-fixation and/or paraffin embedding), Collagen IV was used, which also labels to venules. This implies that unfortunately no direct comparable data to mean arterial size between mice and men could be. For collagen IV IR vasculature, samples of humans were evaluated by counting in stripes of a mean of 3 mm² imaged at 20x through white and grey matter in two sections per region and subject. Samples of human cingulate, temporal, frontal and occipital cortex were averaged and are shown in graphs as “cortex”. In mice values of four sections from five medio-lateral levels in a hemisphere were averaged to an individual mean for the total cerebral cortex and the total hippocampus (grey matter).