Immunohistochemistry and electron microscopy analysis were used to detect amyloid β-(Aβ 1-42 ) and hyperphosphorylated tau (AT8) accumulation and ultrastructural changes in the brain. Memory decline was time-(≤3 months/acute, ≥3 months/progressive) and STZ-icv dosedependent. Morphological changes were manifested as thinning of parietal cortex (≥1 month) and corpus callosum (9 months), and were more pronounced in the 3 mg/kg STZ group. Early neurofibrillary changes (AT8) were detected from 1 month onward in the neocortex, and progressed after 3 months to the hippocampus. Intracellular Aβ 1-42 accumulation was found in the neocortex at 3 months following STZ-icv treatment, while diffuse Aβ 1-42 -positive plaque-like formations were found after 6 months in the neocortex and hippocampus. Ultrastructural changes revealed enlargement of Golgi apparatus, pyknotic nuclei, and timedependent increase in lysosome size, number, and density. Our data provide a staging of cognitive, structural/ultrastructural, and neuropathological markers in the STZ-icv rat model that in many aspects seems to be generally comparable to stages seen in human sAD.

No abstract

Cerebral amyloid angiopathy is manifested as accumulation of amyloid β (Aβ) peptide in the wall of meningeal and cerebral arteries, arterioles and capillaries and is frequently found postmortem in sporadic Alzheimer's disease (sAD) patients. It is difficult to assess when and how cerebral amyloid angiopathy develops and progresses in humans in vivo, which is why animal AD models are used. Streptozotocin-intracerebroventricularly (STZ-icv) treated rats have been recently proposed as the model of sAD which develops insulin resistant brain state preceding Aβ pathology development. Vascular Aβ deposits in the brain of STZ-icv-treated rats (3 months old at the time of icv treatment) were visualized by Thioflavine-S staining, Congo red staining and Aβ immunohistochemistry. Thioflavine-S and Congo red staining revealed diffuse congophilic deposits in the wall of meningeal and cortical blood vessels both 6 and 9 months after the STZ-icv treatment. Preliminary Aβ1-42 and Aβ1-16 immunohistochemistry experiments showed positive staining in blood vessels 3 and 9 months after the STZ-icv treatment, respectively. Results suggest that cerebral amyloid angiopathy observed 6 and 9 months after the STZ-icv treatment seems to be a continuation and progression of the amyloid pathology observed already 3 months following the STZ-icv treatment in this non-transgenic sAD animal model.

No abstract

Hormone therapy (HT) is prescribed during or after menopausal transition to replace the decline in estrogen and progesterone levels. While some studies indicate that estrogen and progesterone depletion in postmenopausal women might carry a significant risk for developing sporadic Alzheimer's disease (sAD), which may be reduced by HT, recent clinical trials oppose this beneficial effect. This review points to possible reasons for these mixed data by considering the issues of both preclinical and clinical trials, in particular the representativeness of animal models, timing of HT initiation, type of HT (different types of estrogen compound, estrogen monotherapy versus estrogen-progesterone combined therapy), mode of drug delivery (subcutaneous, transdermal, oral or intramuscular) and hormone dosage used, as well as the heterogeneity of the postmenopausal population in clinical trials (particularly considering their sAD stage, anti-AD therapy and hysterectomy status). Careful planning of future preclinical and clinical HT interventional studies might help to elucidate the effect of HT on cognitive status in postmenopausal women with sAD, which will eventually contribute to more effective sAD prevention and treatment. Key points:• The influence of hormone therapy (HT) on cognition in postmenopausal women with Alzheimer's disease (AD) is inconclusive mainly due to a translational gap based on inadequate animal models, clinical inter-/intra-group heterogeneity and often incomparable HT study design.• Cognitive outcomes in clinical trials are mostly influenced by HT composition, its dose, timing and route of administration, as well as by ApoE carrier status, co-morbidity and concomitant therapy.•Design of estrogen/progesterone modulators that would optimize cognitive benefits and tailored HT may lead to more successful prevention and treatment of AD in postmenopausal women.

No abstract

No abstract

Thioflavin T and AT8 antibody staining. Results: Resveratrol reduced the level of aggregated phosphorylated tau by 73% as judged by the mean AT8 immunoreactive area (p¼0.017), while the 35% reduction by morin did not reach significance ( Figure, p¼0.14). Neither resveratrol nor morin affected motor function. Conclusions: Oral treatment with resveratrol or possibly with morin may decrease tau hyperphosphorylation. Further animal studies would be informative to explore the possible efficacy of morin or resveratrol for treating tauopathies.