Premium
P4‐152: Sex differences in perivascular tauopathy in the mediobasal tuberal hypothalamus in neurodegenerative diseases in humans
Author(s) -
Dugger Brittany N.,
Uchikado Hirotake,
Ahmed Zshan,
Dickson Dennis W.
Publication year - 2008
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.2008.05.2219
Subject(s) - tauopathy , pathology , median eminence , progressive supranuclear palsy , hypothalamus , biology , alzheimer's disease , neuroscience , medicine , disease , neurodegeneration
Background: The human hypothalamus regulates many metabolic and autonomic functions through the release of hormones into the blood stream. The neurovascular connections between nuclei in this circuitry are critical to neuroendocrine regulation of pituitary gonadotropin secretion. The hypothalamus is known to be pathologically affected in a number of neurodegenerative diseases, including Alzheimer’s disease (AD) (a disease more frequent in women), progressive supranuclear palsy (PSP, no sex difference) and dementia with Lewy bodies (DLB) (a disease more frequent in men). Previous published studies have shown that some AD cases have hypothalamic perivascular neuritic pathology that is argyrophilic and immunopositive for tau protein (“perivascular tauopathy”) and more frequent in men. Hypothalamic perivascular tauopathy has been shown to be independent of AD related neurofibrillary pathology and is characterized by a network of tau-positive, swollen dystrophic neurites adjacent to capillaries of the posterior median eminence and adjacent infundibular nucleus. Methods: In addition to AD (n 90; 47 men), we screened other disorders, including DLB (n 35; 16 men), PSP (n 47; 26 men) and normal elderly controls (n 38; 14 men), for hypothalamic perivascular tauopathy using an phospho-tau antibody (CP13). To further characterize perivascular tauopathy select cases with robust perivascular tauopathy were studied with double labeling immunohistochemistry using phospho-tau and glial (GFAP for astrocytes and Iba-1 for microglia) antibodies. Results: Of the 210 cases screened, 16 had perivascular tauopathy (8%), of which 15 were men. It was detected in 12 with AD (13%), 1 with DLB (3%) and 3 with PSP (6%). The only woman with perivascular tauopathy had PSP. None of normal controls had perivascular tauopathy. When considering all cases together, perivascular tauopathy correlated with Braak neurofibrillary tangle stage in addition to sex. We found no colocalization of the phospho-tau with either of the glial markers in the rubust perivascular tauopathy cases. Conclusions: The present results are consistent with the existence of a sex difference in perivascular neuritic tau pathology in the mediobasal tuberal hypothalamus in age-associated neurodegenerative disorders. This study also noted that perivascular tauopathy was neuronal rather than glial in origin.