ABSTRACT
Alzheimer's disease (AD) is associated with aberrant neuronal activity, which is believed to critically determine disease symptoms. How these activity alterations emerge, how stable they are over time, and whether cellular activity dynamics are affected by the amyloid plaque pathology remains incompletely understood. We here repeatedly recorded the activity from identified neurons in cortex of awake APPPS1 transgenic mice over four weeks during the early phase of plaque deposition using in vivo two-photon calcium imaging. We found that aberrant activity during this stage largely persisted over the observation time. Novel highly active neurons slowly emerged from former intermediately active neurons. Furthermore, activity fluctuations were independent of plaque proximity, but aberrant activity was more likely to persist close to plaques. These results support the notion that neuronal network pathology observed in models of cerebral amyloidosis is the consequence of persistent single cell aberrant neuronal activity, a finding of potential diagnostic and therapeutic relevance for AD.
Subject(s)
Alzheimer Disease/physiopathology , Neurons/physiology , Plaque, Amyloid/physiopathology , Animals , Disease Models, Animal , Female , Male , Mice , Mice, Transgenic , Neurons/pathologyABSTRACT
Case-control study comprised 100 pancreatic cancer patients and the same number of hospital controls individually matched with cases by sex, age and place of residence. According to logistic regression analysis following factors were found to be risk factors for pancreatic cancer: smoking 26 or more cigarettes per day (OR = 43.95, 95% CI = 7.69-192.53), consumption of 5 or more glasses of hard drinks per week (OR = 12.84, 95% CI = 2.13-77.29), coffee consumption during a period exceeding 35 years (OR = 2.50, 95% CI = 1.18-5.28), gall bladder disease in personal history (OR = 4.29, 95% CI = 1.08-16.99) and family history positive on peptic ulcer (OR = 11.71, 95% CI = 0.99-137.98). Two factors appeared to be protective for cancer of pancreas: appendectomy (OR = 0.22, 95% CI = 0.07-0.68) and blood type 0, Rh+ (OR = 0.25, 95% CI = 0.09-0.61).
