Cognitive, neuroimaging, and pathological studies in a patient with Pick's disease.
AuthorsLieberman AP, Trojanowski JQ, Lee VM, Balin BJ, Ding XS, Greenberg J, Morrison D, Reivich M, Grossman M
JournalAnn Neurol
PubMed ID9485069
'We conducted cognitive, imaging, and neuropathological studies on a patient with Pick''s disease. The patient was impaired at interpreting sentences with complex grammatical constructions, differing significantly from control subjects and patients with Alzheimer''s disease (AD). Evaluation of regional brain functioning at rest, with positron emission tomography, revealed reduced left frontal ... More
Abeta and tau form soluble complexes that may promote self aggregation of both into the insoluble forms observed in Alzheimer's disease.
AuthorsGuo JP, Arai T, Miklossy J, McGeer PL,
JournalProc Natl Acad Sci U S A
PubMed ID16446437
To date, there is no reasonable explanation as to why plaques and tangles simultaneously accumulate in Alzheimer's disease (AD). We demonstrate here by Western blotting and ELISA that a stable complex can form between tau and amyloid-beta protein (Abeta). This complex enhances tau phosphorylation by GSK3beta, but the phosphorylation then ... More
Neurodegeneration in heterozygous Niemann-Pick type C1 (NPC1) mouse: implication of heterozygous NPC1 mutations being a risk for tauopathy.
AuthorsYu W, Ko M, Yanagisawa K, Michikawa M,
JournalJ Biol Chem
PubMed ID15919659
Niemann-Pick type C1 (NPC1) disease is an autosomal recessive, fatal disorder characterized by a defect in cholesterol trafficking and progressive neurodegeneration. The disease is predominantly caused by mutations in the NPC1 gene; however, it has been assumed that heterozygous NPC1 mutations do not cause any symptoms. Here we demonstrate that ... More
Proteolysis of non-phosphorylated and phosphorylated tau by thrombin.
AuthorsArai T, Guo JP, McGeer PL,
JournalJ Biol Chem
PubMed ID15542598
The microtubule-associated protein tau aggregates intracellularly by unknown mechanisms in Alzheimer's disease and other tauopathies. A contributing factor may be a failure to break down free cytosolic tau, thus creating a surplus for aggregation, although the proteases that degrade tau in brain remain unknown. To address this issue, we prepared ... More
Fyn phosphorylates human MAP-2c on tyrosine 67.
AuthorsZamora-Leon SP, Bresnick A, Backer JM, Shafit-Zagardo B,
JournalJ Biol Chem
PubMed ID15536091
The Src homology 3 (SH3) domain of Fyn binds to a conserved PXXP motif on microtubule-associated protein-2. Co-transfections into COS7 cells and in vitro kinase assays performed with Fyn and wild-type, or mutant MAP-2c, determined that Fyn phosphorylated MAP-2c on tyrosine 67. The phosphorylation generated a consensus sequence for the ... More
Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or memory impairment in mice.
AuthorsWang B, Tanaka K, Ji B, Ono M, Fang Y, Ninomiya Y, Maruyama K, Izumi-Nakajima N, Begum N, Higuchi M, Fujimori A, Uehara Y, Nakajima T, Suhara T, Ono T, Nenoi M,
Journal
PubMed ID23908553
The cause and progression of Alzheimer's disease (AD) are poorly understood. Possible cognitive and behavioral consequences induced by low-dose radiation are important because humans are exposed to ionizing radiation from various sources. Early transcriptional response in murine brain to low-dose X-rays (100 mGy) has been reported, suggesting alterations of molecular ... More
Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology.
Neurofibrillary tangles (NFTs) are composed of abnormal aggregates of the cytoskeletal protein tau. Together with amyloid beta (Abeta) plaques and neuronal and synaptic loss, NFTs constitute the primary pathological hallmarks of Alzheimer disease (AD). Recent evidence also suggests that caspases are activated early in the progression of AD and may ... More
The neuropathology of a chromosome 17-linked autosomal dominant parkinsonism and dementia ("pallido-ponto-nigral degeneration").
A group of similar autosomal dominant hereditary neurodegenerative disorders have been linked to chromosome 17 in thirteen kindreds. One of these disorders, known as pallido-ponto-nigral degeneration (PPND), is characterized by extensive degeneration of the globus pallidus and substantia nigra as well as accumulation of abnormally phosphorylated tau proteins. The authors ... More
Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17.
AuthorsClark LN, Poorkaj P, Wszolek Z, Geschwind DH, Nasreddine ZS, Miller B, Li D, Payami H, Awert F, Markopoulou K, Andreadis A, D'Souza I, Lee VM, Reed L, Trojanowski JQ, Zhukareva V, Bird T, Schellenberg G, Wilhelmsen KC
JournalProc Natl Acad Sci U S A
PubMed ID9789048
Pallido-ponto-nigral degeneration (PPND) is one of the most well characterized familial neurodegenerative disorders linked to chromosome 17q21-22. These hereditary disorders are known collectively as frontotemporal dementia (FTD) and parkinsonism linked to chromosome 17 (FTDP-17). Although the clinical features and associated regional variations in the neuronal loss observed in different FTDP-17 ... More