The major defining pathological hallmarks of Alzheimer's disease (AD) are the accumulations of Abeta in senile plaques and hyperphosphorylated tau in neurofibrillary tangles and neuropil threads. Recent studies indicate that rather than these insoluble lesions, the soluble Abeta oligomers and hyperphosphorylated tau are the toxic agents of AD pathology. Such pathological protein species are accompanied by cytoskeletal changes, mitochondrial dysfunction, Ca2+ dysregulation, and oxidative stress. In this review, we discuss how the binding of Abeta to various integrins, defects in downstream focal adhesion signaling, and activation of cofilin can impact mitochondrial dysfunction, cytoskeletal changes, and tau pathology induced by Abeta oligomers. Such pathological consequences can also feedback to further activate cofilin to promote cofilin pathology. We also suggest that the mechanism of Abeta generation by the endocytosis of APP is mechanistically linked with perturbations in integrin-based focal adhesion signaling, as APP, LRP, and beta-integrins are physically associated with each other.
Alzheimer Disease ; Amyloid ; Cytoskeleton ; Endocytosis ; Focal Adhesions ; Integrins ; Mitochondria ; Neurofibrillary Tangles ; Neuropil Threads ; Oxidative Stress ; Plaque, Amyloid

PURPOSE: To compare the variable inflammatory parameters of acute pyelonephritis patients treated with inpatient therapy at 13 hospitals, according to the age and gender distributions. MATERIALS AND MATHODS: A total of 3,544 medical records of patients with confirmed acute pyelonephritis, and admitted to hospital between January 2000 and December 2005, were retrospectively analyzed. RESULTS: The mean age of the patients was 43.2+/-16.2 years old, with a male:female ratio of 1 : 5.1. The average duration of hospital admission was 7.9+/-5.3 days. Underlying diseases were found in 23.0% (749/3,252 patient), largely due to diabetes (35.1%). Radiological abnormal findings were found in 13.7%. The leukocyte count, ratio of segmented form, erythrocyte sedimentation rate (ESR), c-reactive protein, pyuria, positive blood culture, positive urine culture were 11,014+/-5,778/mm(3), 74.8+/-14.5%, 44.0+/-32.0 mm/hr, 12.4+/-9.3mg/dl, 83.9%, 10.5% and 46.7%, respectively. E. coli grow in 79% of the urine culture positive patients. In a comparison of 3 age groups (<40 years, 40-60 years, >61 years), the elderly patients had a greater number of underlying diseases and more pathogens in cultured blood. When divided into males and females, the elderly male patients had more pathogen in cultured urine, but contrary to the male patients, the elderly female patients had elevated leukocyte count and erythrocyte sedimentation rate. Also, the old patient group had more resistance to ampicillin when they had E. coli as the uropathogen (p=0.021). Patients with higher ESR required longer hospital admission periods. CONCLUSIONS: It was found that variable clinical parameters of acute pyelonephritis patients treated with inpatient therapy differed according to both gender and age group in Korea. Therefore, these factors should be taken into account in the treatment plan.
Aged ; Ampicillin ; Blood Sedimentation ; C-Reactive Protein ; Female ; Humans ; Inpatients ; Korea ; Leukocyte Count ; Male ; Medical Records ; Pyelonephritis* ; Pyuria ; Retrospective Studies