Effects of Alzheimer's disease on different cortical layers: the role of intrinsic differences in Abeta susceptibility.

Effects of Alzheimer's disease on different cortical layers: the role of intrinsic differences in Abeta susceptibility. Research Abstract Details 

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Effects of Alzheimer's disease on different cortical layers: the role of intrinsic differences in Abeta susceptibility. Abstract Text:

Rita R Romito-DiGiacomo,Harry Menegay,Samantha A Cicero,Karl Herrup,

Alzheimer's disease is late life dementia associated with significant neurodegeneration in both cortical and subcortical regions. During the approximately 10 year course of the disease, neurons are lost in a progressive pattern that is relatively consistent among individuals. One example of this is the progression of disease pathology found in both the neocortex and archicortex. In these structures, the earliest problems can be found in superficial cortical layers (II-IV), whereas later the disease advances to involve the deeper cortical layers (V-VI). It is unclear whether these apparent differences in sensitivity are intrinsic to the neurons or imposed by external factors such as the pattern of connections. We used beta-amyloid (Abeta) peptide treatment of cultured mouse neurons as our model system. We show first that, as in hippocampus, dissociated cultures of embryonic cortical neurons are biased toward the survival of cells that were finishing division in the ventricular zone at the time of harvest. Thus, embryonic day 13.5 (E13.5) cultures contain primarily deep-layer neurons whereas E16.5 cultures contain cells destined for upper layers. We use this cell-type specific segregation to our advantage and show, using both differences in gene expression profiles and Abeta survival curves, that deeper layer neurons are significantly more resistant to the toxic effects of Abeta than are cells from the more superficial strata. This suggests that an intrinsic underlying biology drives at least part of the AD progression pattern and that the time of harvest is a crucial variable in the interpretation of any cortical culture experiment.

Effects of Alzheimer's disease on different cortical layers: the role of intrinsic differences in Abeta susceptibility. Publishing Authors By Initials

RR Romito-DiGiacomo,H Menegay,SA Cicero,K Herrup,

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Effects of Alzheimer's disease on different cortical layers: the role of intrinsic differences in Abeta susceptibility. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of neuroscience : the official journal

VOLUME: 27

Page Numbers: 8496-504

Journal Abbreviation: J. Neurosci.

ISSN: 1529-2401

DAY: 8

MONTH: Aug

YEAR: 2007

Effects of Alzheimer's disease on different cortical layers: the role of intrinsic differences in Abeta susceptibility. Information

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LANGUAGE: eng

NlmUniqueID: 8102140

Effects of Alzheimer's disease on different cortical layers: the role of intrinsic differences in Abeta susceptibility. Keywords Mesh Terms:

KEYWORDS: Pregnancy

MESH TERMS: pathology

Chemical & Substance for Abstract: Effects of Alzheimer's disease on different cortical layers: the role of intrinsic differences in Abeta susceptibility. Information

Substance Name: Amyloid beta-Protein

Registry Number: 0

Grant and Affiliation Information for Effects of Alzheimer's disease on different cortical layers: the role of intrinsic differences in Abeta susceptibility.

AFFILIATION: Department of Neuroscience, Alzheimer Research Laboratory, Case School of Medicine, Cleveland, Ohio 44106, USA.

Country: United States

AGENCY: United States NINDS

GRANT: NS20591

ACRONYM: NS

MEDLINETA: J Neurosci

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