Subicular Dendritic Arborization in Alzheimer's Disease Correlates with Neurofibrillary Tangle Density

Falke, Eric; Nissanov, Jonathan; Mitchell, Thomas W.; Bennett, David A.; Trojanowski, John Q.; Arnold, Steven E.

doi:10.1016/s0002-9440(10)63518-3

Cited by 79 publications

(47 citation statements)

References 24 publications

(31 reference statements)

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“…In AD, Ͼ90% of cortical tau aggregation localizes to neuropil threads and dystrophic neurites associated with neuritic plaques, indicating that most tau aggregation occurs in specialized processes rather than in cell bodies (73). These aggregates may affect end points other than viability that are nonetheless important for disease progression, including retraction and loss of dendritic arbors (74) and synaptic contacts (75). For example, intracellular aggregates formed from polyglutamine repeats can inhibit processes especially important for neuronal homeostasis such as axoplasmic flow (76).…”

Section: Discussionmentioning

confidence: 99%

Tau Aggregation and Toxicity in a Cell Culture Model of Tauopathy

Bandyopadhyay

Yin

et al. 2007

Journal of Biological Chemistry

121

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Intracellular aggregation of the microtubule-associated protein tau into filamentous inclusions is a defining characteristic of Alzheimer disease. Because appearance of tau-aggregate bearing lesions correlates with both cognitive decline and neurodegeneration, it has been hypothesized that tau aggregation may be directly toxic to cells that harbor them. Testing this hypothesis in cell culture has been complicated by the resistance of full-length tau isoforms to aggregation over experimentally tractable time periods. To overcome this limitation, a smallmolecule agonist of the tau aggregation reaction, Congo red, was used to drive aggregation within HEK-293 cells expressing fulllength tau isoform htau40. Formation of detergent-insoluble aggregates was both time and agonist concentration dependent. At 10 M Congo red, detergent-insoluble aggregates appeared with pseudo-first order kinetics and a half-life of approximately 5 days. By 7 days in culture, total tau levels increased 2-fold, with ϳ30% of total tau converted into detergent-insoluble aggregates. Agonist addition also led to rapid losses in the tubulin binding activity of tau, although tau was not hyperphosphorylated as judged by occupancy of phosphorylation sites Ser 396 / Ser 404 . Tau aggregation was associated with decreased viability as detected by ToPro-3 uptake. The results, which establish a new approach for analysis of tau aggregation in cells independent of tau hyperphosphorylation, suggest that conformational changes associated with aggregation are incompatible with microtubule binding, and that toxicity associated with intracellular tau aggregation is not acute but develops over a period of days.

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Section: Discussionmentioning

confidence: 99%

Tau Aggregation and Toxicity in a Cell Culture Model of Tauopathy

Bandyopadhyay

Yin

et al. 2007

Journal of Biological Chemistry

121

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“…Several putative indices of neural reserve are also being quantifi ed in 20-m sections from the same brain regions, including neu-rons with cresyl violet stain for Nissl substances, and M13, a mouse monoclonal antibody that identifi es all isoforms of MAP2 for dendrites [72] . Finally, synaptic proteins, including synaptophysin, VAMP, SNAP-25, syntaxin and CDCrel-1, are identifi ed by ELISA [73] .…”

Section: Postmortem Indicesmentioning

confidence: 99%

The Rush Memory and Aging Project: Study Design and Baseline Characteristics of the Study Cohort

et al. 2005

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The long-term objective of the Rush Memory and Aging Project is to identify the postmortem indices linking genetic and environmental risk factors to the development of Alzheimer’s disease (AD). The overall study design involves a detailed assessment of risk factors for AD in older persons without known dementia who agree to annual clinical evaluation and organ donation at the time of death. In contrast to other clinical-pathologic studies which are conducted on special populations, the Rush Memory and Aging Project enrolled a cohort with much greater diversity in terms of educational attainment, in addition to gender, race, and ethnicity. From September of 1997 through April of 2005, more than 1,000 older persons without known dementia from more than 30 residential facilities across the Chicago metropolitan area agreed to participate. Their mean age was 81 years, about a third had 12 or fewer years of education, a third were men, and about 10% were members of a racial or ethnic minority group. More than 950 already have completed their baseline clinical evaluation.

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“…Abnormal neuronal activity in such patients might cause local disruption to ion homeostasis in the brain. Also, recent studies on Alzheimer's disease have shown that dendritic arborization would be affected by the presence of neurofibrillary tangles (Falke et al 2003), bringing about an early abnormality in the tissue myelination (Desai et al 2009). These changes in myelin distribution can be detected through analysis of the conductivity profile, either invasively in laboratory animals (e.g., using our methodology) or in practical situations at a clinic in humans, using impedance tomography (Cheney et al 1999).…”

Section: Future Directionsmentioning

confidence: 99%

An Evaluation of the Conductivity Profile in the Somatosensory Barrel Cortex of Wistar Rats

Goto

Hatanaka

Ogawa

et al. 2010

Journal of Neurophysiology

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Microelectrode arrays used to record local field potentials from the brain are being built with increasingly more spatial resolution, ranging from the initially developed laminar arrays to those with planar and three-dimensional (3D) formats. In parallel with such development in recording techniques, current source density (CSD) analyses have recently been expanded up to the continuous-3D form. Unfortunately, the effect of the conductivity profile on the CSD analysis performed with contemporary microelectrode arrays has not yet been evaluated and most of the studies assumed it was homogeneous and isotropic. In this study, we measured the conductivity profile in the somatosensory barrel cortex of Wistar rats. To that end, we combined multisite electrophysiological data recorded with a homemade assembly of silicon-based probes and a nonlinear least-squares algorithm that implicitly assumed that the cerebral cortex of rodents could be locally approximated as a layered anisotropic spherical volume conductor. The eccentricity of the six cortical layers in the somatosensory barrel cortex was evaluated from postmortem histological images. We provided evidence for the local spherical character of the entire barrels field, with concentric cortical layers. We found significant laminar dependencies in the conductivity values with radial/tangential anisotropies. These results were in agreement with the layer-dependent orientations of myelinated axons, but hardly related to densities of cells. Finally, we demonstrated through simulations that ignoring the real conductivity profile in the somatosensory barrel cortex of rats caused considerable errors in the CSD reconstruction, with pronounced effects on the continuous-3D form and charge-unbalanced CSD. We concluded that the conductivity profile must be included in future developments of CSD analysis, especially for rodents.

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Subicular Dendritic Arborization in Alzheimer's Disease Correlates with Neurofibrillary Tangle Density

Cited by 79 publications

References 24 publications

Tau Aggregation and Toxicity in a Cell Culture Model of Tauopathy

Tau Aggregation and Toxicity in a Cell Culture Model of Tauopathy

The Rush Memory and Aging Project: Study Design and Baseline Characteristics of the Study Cohort

An Evaluation of the Conductivity Profile in the Somatosensory Barrel Cortex of Wistar Rats

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