Alzheimer Disease: McKhann GM

McKhann GM, Albert MS, Grossman M, Miller B, Dickson D, Trojanowski JQ, Anonymous00019. · Department of Neurology, Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University School of Medicine, 338 Krieger Hall, 3400 N Charles St, Baltimore, MD 21218-2685, USA. · Arch Neurol. · Pubmed #11708987 links to  free full text

Abstract: An international group of clinical and basic scientists participated in the Frontotemporal Dementia and Pick's Disease Criteria Conference at the National Institutes of Health in Bethesda, Md, on July 7, 2000, to reassess clinical and neuropathological criteria for the diagnosis of frontotemporal dementia (FTD). Previous criteria for FTD have primarily been designed for research purposes. The goal of this meeting was to propose guidelines that would enable clinicians (particularly neurologists, psychiatrists, and neuropsychologists) to recognize patients with FTD and, if appropriate, to expedite their referral to a diagnostic center. In addition, recommendations for the neuropathological criteria of FTD were reviewed, relative to classical neuropathology and modern molecular biology.

Du H, Guo L, Fang F, Chen D, Sosunov AA, McKhann GM, Yan Y, Wang C, Zhang H, Molkentin JD, Gunn-Moore FJ, Vonsattel JP, Arancio O, Chen JX, Yan SD. · Department of Surgery, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, New York 10032, USA. · Nat Med. · Pubmed #18806802 No free full text.

Abstract: Cyclophilin D (CypD, encoded by Ppif) is an integral part of the mitochondrial permeability transition pore, whose opening leads to cell death. Here we show that interaction of CypD with mitochondrial amyloid-beta protein (Abeta) potentiates mitochondrial, neuronal and synaptic stress. The CypD-deficient cortical mitochondria are resistant to Abeta- and Ca(2+)-induced mitochondrial swelling and permeability transition. Additionally, they have an increased calcium buffering capacity and generate fewer mitochondrial reactive oxygen species. Furthermore, the absence of CypD protects neurons from Abeta- and oxidative stress-induced cell death. Notably, CypD deficiency substantially improves learning and memory and synaptic function in an Alzheimer's disease mouse model and alleviates Abeta-mediated reduction of long-term potentiation. Thus, the CypD-mediated mitochondrial permeability transition pore is directly linked to the cellular and synaptic perturbations observed in the pathogenesis of Alzheimer's disease. Blockade of CypD may be a therapeutic strategy in Alzheimer's disease.

Selnes OA, Grega MA, Bailey MM, Pham L, Zeger S, Baumgartner WA, McKhann GM. · Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Ann Thorac Surg. · Pubmed #18036903 No free full text.

Abstract: BACKGROUND: Cardiopulmonary bypass has been implicated in the late cognitive decline that has been reported after coronary artery bypass graft (CABG) surgery. Because most studies did not include a control group, a causal link of such decline with the use of cardiopulmonary bypass has not been established. METHODS: We compared changes in cognitive performance from baseline to 3 years in patients undergoing on-pump CABG (n = 152) with those of three control groups: patients with off-pump surgery (n = 75); with diagnosed coronary artery disease but no surgery (n = 99); and without coronary artery disease risk factors (n = 69). Neuropsychological performance was assessed by standardized tests of attention, language, verbal and visual memory, visuospatial, executive function, and psychomotor and motor speed. RESULTS: Relative to their baseline performance, no group had significantly lower performance at 36 months for any of the cognitive domains. From 12 to 36 months, there were no statistically significant differences in the degree of change between the on- and off-pump surgery groups. There was a trend toward mild decline in some cognitive domains, but overall differences among groups in degree of change over time were not statistically significant. CONCLUSIONS: We found a mild but nonsignificant trend toward late postoperative cognitive decline for all study groups with coronary artery disease, but no significant differences in the degree of late postoperative cognitive decline after on-pump compared with off-pump surgery. These findings suggest that previously reported late decline after bypass surgery is not specific to use of cardiopulmonary bypass.