OBJECTIVE: We hypothesized that prominent pulvinar hypointensity in brain MRI represents the disease process due to iron accumulation in Alzheimer disease (AD). We aimed to determine whether or not the pulvinar signal intensity (SI) on the fluid-attenuated inversion recovery (FLAIR) sequences at 3.0T MRI differs between AD patients and normal subjects, and also whether the pulvinar SI is correlated with the T2* map, an imaging marker for tissue iron, and a cognitive scale. MATERIALS AND METHODS: Twenty one consecutive patients with AD and 21 age-matched control subjects were prospectively included in this study. The pulvinar SI was assessed on the FLAIR image. We measured the relative SI ratio of the pulvinar to the corpus callosum. The T2* values were calculated from the T2* relaxometry map. The differences between the two groups were analyzed, by using a Student t test. The correlation between the measurements was assessed by the Pearson's correlation test. RESULTS: As compared to the normal white matter, the FLAIR signal intensity of the pulvinar nucleus was significantly more hypointense in the AD patients than in the control subjects (p < 0.01). The pulvinar T2* was shorter in the AD patients than in the control subjects (51.5 +/- 4.95 ms vs. 56.5 +/- 5.49 ms, respectively, p = 0.003). The pulvinar SI ratio was strongly correlated with the pulvinar T2* (r = 0.745, p < 0.001). When controlling for age, only the pulvinar-to-CC SI ratio was positively correlated with that of the Mini-Mental State Examination (MMSE) score (r = 0.303, p < 0.050). Conversely, the pulvinar T2* was not correlated with the MMSE score (r = 0.277, p = 0.080). CONCLUSION: The FLAIR hypointensity of the pulvinar nucleus represents an abnormal iron accumulation in AD and may be used as an adjunctive finding for evaluating AD.
Aged ; Alzheimer Disease/*metabolism/*pathology ; Female ; Humans ; Iron/*metabolism ; *Magnetic Resonance Imaging ; Male ; Pulvinar/metabolism/*pathology

Alzheimer Disease/pathology* ; Animals ; C9orf72 Protein/metabolism* ; Mice ; Microglia/pathology* ; Neuronal Plasticity ; Neurons/pathology* ; Synapses/pathology*

Autophagy is a dynamic cellular pathway involved in the turnover of proteins, protein complexes, and organelles through lysosomal degradation. The integrity of postmitotic neurons is heavily dependent on high basal autophagy compared to non-neuronal cells as misfolded proteins and damaged organelles cannot be diluted through cell division. Moreover, neurons contain the specialized structures for intercellular communication, such as axons, dendrites and synapses, which require the reciprocal transport of proteins, organelles and autophagosomes over significant distances from the soma. Defects in autophagy affect the intercellular communication and subsequently, contributing to neurodegeneration. The presence of abnormal autophagic activity is frequently observed in selective neuronal populations afflicted in common neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. These observations have provoked controversy regarding whether the increase in autophagosomes observed in the degenerating neurons play a protective role or instead contribute to pathogenic neuronal cell death. It is still unknown what factors may determine whether active autophagy is beneficial or pathogenic during neurodegeneration. In this review, we consider both the normal and pathophysiological roles of neuronal autophagy and its potential therapeutic implications for common neurodegenerative diseases.
Alzheimer Disease/metabolism/pathology/physiopathology ; Animals ; Autophagy/*physiology ; Humans ; Huntington Disease/metabolism/pathology/physiopathology ; Models, Biological ; Neurodegenerative Diseases/metabolism/*pathology/physiopathology ; Neurons/*cytology ; Parkinson Disease/metabolism/pathology/physiopathology

Atomic force microscope (AFM) has become a well-established technique for biological sample imaging under physiological conditions. The unique capacity to produce nanometer scale resolution images with simple specimen preparation enables AFM to serve as a powerful tool in neurobiology research. Extensive studies suggest that the conversion of beta-amyloid (Abeta) peptide from soluble forms into fibrillar structure is a key factor in the pathogenesis of Alzheimer's disease (AD). AFM has provided useful insights at all stages of Abeta fibrillization, thus making therapeutic strategy possible. In this brief review, the principles and techniques of AFM and their effects on the pathogenetic study of AD, especially on the study of Abeta and Abeta oligomer are outlined.
Alzheimer Disease ; metabolism ; pathology ; Amyloid beta-Peptides ; metabolism ; Humans ; Microscopy, Atomic Force

The injury of exogenous formaldehyde and its merchanism have attracted wide attention from researchers. The latest study found that mammals have a whole system for generating and clearning formaldehyde. However, the imbalance on the system for generating and clearning formaldehyde for various reasons will cause abnormal accumulation of endogenous formaldehyde in vivo, which is closely related to learning diability and memory dysfunction. The increase in endogenous formaldehyde concentration may be one of factors inducing such neurodegenerative diseases as Alzheimer's disease. The study on the relationship between endogenous formaldehyde and such neurodegenerative diseases as Alzheimer's disease is of great significance and can provide new thoughts for preventing and treating Alzheimer's disease with traditional Chinese medicines.
Alzheimer Disease ; drug therapy ; metabolism ; pathology ; Animals ; Drugs, Chinese Herbal ; therapeutic use ; Formaldehyde ; metabolism ; Humans

OBJECTIVETo study the expression of tau-related protein in spinal cord of Chinese patients with Alzheimer's disease.

METHODSGallays-Braak stain and immunohistochemical study for tau protein (AT8) were carried out in the spinal cord tissue (T2, T8, T10, L2 and S2 segments) of 3 Chinese patients with Alzheimer's disease. Seven age-matched cases without evidence of dementia or neurologic disease were used as controls.

RESULTSNeurofibrillary tangles were identified in the neurons of anterior horn in 2 Alzheimer's disease cases but none was observed in the controls. Tau-positive axons and astroglia were detected in all Alzheimer's disease cases. Tau immunoreactivity in spinal cord of the patients correlated with that in brain tissue.

CONCLUSIONThe expression of tau-related protein is demonstrated in the spinal cord of Alzheimer's disease patients suggesting that axonal transport defect may play a role in the pathogenesis of Alzheimer's disease.

Aged ; Alzheimer Disease ; metabolism ; pathology ; Axonal Transport ; Axons ; metabolism ; pathology ; Humans ; Male ; Neurofibrillary Tangles ; metabolism ; pathology ; Phosphorylation ; Spinal Cord ; metabolism ; pathology ; tau Proteins ; metabolism

OBJECTIVETo observe the cellular uptake of beta amyloid protein (Abeta) by cultured human neuroblastoma (SH-SY5Y) cells and the location of Abeta in the subcellular structures.

METHODSThe time course of cellular uptake of Abeta1-42-fluo in the SH-SY5Y cells was observed directly under laser scanning confocal microscope (LSCM). Image analysis was conducted to compare the differences of cellular Abeta uptake after treatment of the cells with different concentrations of extracellular Abeta for 24 h. Multiple immunofluorescence staining was employed to identify the location of Abeta in the subcellular structures.

RESULTSSH-SY5Y cells showed Abeta internalization after incubation with Abeta1-42-fluo (200 nmol/L) for 1 h, and the quantity of Abeta uptake was time-dependent. A higher concentration of extracellular Abeta1-42-fluo resulted in increased Abeta uptake, which differed significantly between the 3 groups with treatment at different concentrations (P<0.01 or 0.05). Immunofluorescence staining revealed a co-localization of part of the Abeta and Lamp-1 (a lysosome marker) in the cytosome.

CONCLUSIONSH-SY5Y cells can clear Abeta through a time- and dose-dependent cellular uptake mechanism. Part of the Abeta uptaken in the cytoplasm is located in the lysosome .

Alzheimer Disease ; metabolism ; Amyloid beta-Peptides ; metabolism ; Cell Line, Tumor ; Humans ; Neuroblastoma ; metabolism ; pathology ; Peptide Fragments ; metabolism

Review the research and development status that acupuncture and Chinese medicine are treating Alzheimer disease (AD) for recent year. From pathogenesy of AD view explain the interventional effects and mechanisms of traditional Chinese medicine on Alzheimer disease. Summarize the main species of Chinese medicine compound and components playing roles. Prefer that traditional Chinese medicine has multiple effects and this will be the development direction of it on Alzheimer disease.
Alzheimer Disease ; drug therapy ; metabolism ; pathology ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; methods

The mammalian target of rapamycin(mTOR)is a serine/threonine protein kinase that regulates protein synthesis and degradation,cytoskeletal formation,and cell longevity.Autophagy,a catabolic process necessary for the maintenance of intracellular homeostasis,is essential for cell survival,whereas mTOR is the crucial regulator of autophagy.Alzheimer's disease(AD)is the most common cause of progressive dementia in the elderly.It has been shown that disorders of mTOR and autophagy signaling pathways are closely related to AD.In the present review,we describe the regulatory roles of mTOR signaling and autophagy pathway in AD brain and introduce drugs for AD acting via modulation of autophagy and mTOR.
Alzheimer Disease ; pathology ; Autophagy ; Humans ; Signal Transduction ; TOR Serine-Threonine Kinases ; metabolism

The physiological functions of endogenous amyloid-β (Aβ), which plays important role in the pathology of Alzheimer's disease (AD), have not been paid enough attention. Here, we review the multiple physiological effects of Aβ, particularly in regulating synaptic transmission, and the possible mechanisms, in order to decipher the real characters of Aβ under both physiological and pathological conditions. Some worthy studies have shown that the deprivation of endogenous Aβ gives rise to synaptic dysfunction and cognitive deficiency, while the moderate elevation of this peptide enhances long term potentiation and leads to neuronal hyperexcitability. In this review, we provide a new view for understanding the role of Aβ in AD pathophysiology from the perspective of physiological meaning.
Humans ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Long-Term Potentiation ; Synaptic Transmission/physiology* ; Hippocampus