Angiotensin II Immunoreactivity in the Human Striatum and Hippocampus of Elderly Controls and Patients with Senile Dementia of the Alzheimer Type and Multi-Infarct Dementia

Abstract

The distribution of angiotensin II (A II) immunoreactivity in the postmortem human corpus striatum was studied in control cases and in patients with senile dementia of the Alzheimer type (SDAT) and multi-infarct dementia (MID). Additionally A II immunoreactivity was examined in the hippocampus of control and SDAT patients. A II-immunopositive cellular structures found in the striatum were the large neurons and vesiculated fibers in the globus pallidus (GP), especially in the dorsal parts, and some aspiny neurons in the putamen. Changes in the cell morphology marked the neurons in the GP of SDAT patients. In the MID cases only a few A II-immunopositive fibers and no cell somata were present in the GP. An extracellular, perivascular A II-staining pattern, which was found only in 1 control case, was common to all SDAT and MID patients. A II-immunopositive cellular structures found in the hippocampus included distorted neuronal processes and vesiculated fibers, which were partly coexisting with neuritic plaques as shown by the double labeling with thioflavin. The perivascular A II staining was also observed in the hippocampus, which was more predominant in SDAT cases. The definition of these two A II-immunopositive cell types in human corpus striatum suggests that A II may be involved in local neuronal or projection pathways. Possibly A II participates in the development of cerebrovascular pathologies in elderly control and demented brains.

The Role of the Brain Renin-Angiotensin System in Neurodegenerative Disorders

“…In a next step the synthesis of several RAS components, namely renin and angiotensinogen, within the brain were confirmed by the identification of their messenger RNA sequences [30,31]. In addition, in human brain Ang II immunoreactivity has been shown in the basal ganglia, cortex, hypothalamus, thalamus, brainstem and cerebellum [32][33][34], and Ang binding sites are present in the forebrain, substantia nigra, basal ganglia, cerebellum, cortex, thalamus and hippocampus [35][36][37]. Thus, Ang II in the brain has been suggested to act as a neurotransmitter regulating thirst, drinking, antidiuretic hormone secretion, fascilitating vasopressor effects and hormone secretion such as adrenocorticotrophic and luteinizing hormones [38,39].…”

“…Several studies have investigated the AD-related RAS alterations in the brain [33,34,81,82,94]. ACE activity was found to be elevated in the cortex [34,81,82], medial hippocampus, parahippocampal gyrus and caudate nucleus of AD patients [81].…”

“…Since the supressing effect of Ang II on acetylcholine release is well established [40,41], and acetylcholine is one of the major neurotransmitter systems heavily implicated in AD pathology, the enhanced RAS activity may represent an additional factor contributing to cognitive impairment in AD. Interestingly, neurons containing Ang II found in the striatum and hippocampus of AD patients were found to participate in AD-related plaque formations, and Ang II immunoreactive neurons in those patients were mostly distorted showing neurodegenerative changes [33]. Ang II acting as a neuropeptide in those brain regions may be directly involved in AD pathology.…”

Immunohistochemical Localization of Angiotensin-Converting Enzyme, Angiotensin II and AT1 Receptor in Human Ocular Tissues

“…It is now well known that all components of the RAS exist in the brain [7]. Besides its action as a vasoactive peptide, AngII, as the active component of the RAS, exerts modulatory actions on neurons in the CNS [8,9].…”

“…The immunohistochemical localizations of AngII and ACE in different brain regions has been well studied in rats [10][11][12] and humans [8,9,13], in particular the corti-cal distribution of the AT1 receptor (AT1), a 7-transmembrane receptor coupled to phospholipase C, calcium and cAMP second-messenger systems, which mediates most of the actions of AngII including blood pressure regulation and growth-promoting effects [2,8,14,15].…”