Gene expression correlates of neurofibrillary tangles in Alzheimer's disease

Travis Dunckley; Thomas G. Beach; Keri E. Ramsey; Andrew Grover; Diego Mastroeni; Douglas G. Walker; Bonnie J. LaFleur; Keith D. Coon; Kevin M. Brown; Richard Caselli; Walter Kukull; Roger Higdon; Daniel McKeel; John C. Morris; Christine Hulette; Donald Schmechel; Eric M. Reiman; Joseph Rogers; Dietrich A. Stephan

doi:10.1016/j.neurobiolaging.2005.08.013

Gene expression correlates of neurofibrillary tangles in Alzheimer's disease

Travis Dunckley, Thomas G. Beach, Keri E. Ramsey, Andrew Grover, Diego Mastroeni, Douglas G. Walker, Bonnie J. LaFleur, Keith D. Coon, Kevin M. Brown, Richard Caselli, Walter Kukull, Roger Higdon, Daniel McKeel, John C. Morris, Christine Hulette, Donald Schmechel, Eric M. Reiman, Joseph Rogers, Dietrich A. Stephan

Neurology

Research output: Contribution to journal › Article › peer-review

105 Scopus citations

Abstract

Neurofibrillary tangles (NFT) constitute one of the cardinal histopathological features of Alzheimer's disease (AD). To explore in vivo molecular processes involved in the development of NFTs, we compared gene expression profiles of NFT-bearing entorhinal cortex neurons from 19 AD patients, adjacent non-NFT-bearing entorhinal cortex neurons from the same patients, and non-NFT-bearing entorhinal cortex neurons from 14 non-demented, histopathologically normal controls (ND). Of the differentially expressed genes, 225 showed progressively increased expression (AD NFT neurons > AD non-NFT neurons > ND non-NFT neurons) or progressively decreased expression (AD NFT neurons < AD non-NFT neurons < ND non-NFT neurons), raising the possibility that they may be related to the early stages of NFT formation. Immunohistochemical studies confirmed that many of the implicated proteins are dysregulated and preferentially localized to NFTs, including apolipoprotein J, interleukin-1 receptor-associated kinase 1, tissue inhibitor of metalloproteinase 3, and casein kinase 2, beta. Functional validation studies are underway to determine which candidate genes may be causally related to NFT neuropathology, thus providing therapeutic targets for the treatment of AD.

Original language	English (US)
Pages (from-to)	1359-1371
Number of pages	13
Journal	Neurobiology of aging
Volume	27
Issue number	10
DOIs	https://doi.org/10.1016/j.neurobiolaging.2005.08.013
State	Published - Oct 2006

Keywords

Alzheimer's disease
Dementia
Gene expression
Laser capture microdissection
Microarray
NFT
Neurodegeneration
Neurofibrillary tangles

ASJC Scopus subject areas

Clinical Neurology
Geriatrics and Gerontology
Aging
General Neuroscience
Developmental Biology

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10.1016/j.neurobiolaging.2005.08.013

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Dunckley, T., Beach, T. G., Ramsey, K. E., Grover, A., Mastroeni, D., Walker, D. G., LaFleur, B. J., Coon, K. D., Brown, K. M., Caselli, R., Kukull, W., Higdon, R., McKeel, D., Morris, J. C., Hulette, C., Schmechel, D., Reiman, E. M., Rogers, J., & Stephan, D. A. (2006). Gene expression correlates of neurofibrillary tangles in Alzheimer's disease. Neurobiology of aging, 27(10), 1359-1371. https://doi.org/10.1016/j.neurobiolaging.2005.08.013

Dunckley, T, Beach, TG, Ramsey, KE, Grover, A, Mastroeni, D, Walker, DG, LaFleur, BJ, Coon, KD, Brown, KM, Caselli, R, Kukull, W, Higdon, R, McKeel, D, Morris, JC, Hulette, C, Schmechel, D, Reiman, EM, Rogers, J & Stephan, DA 2006, 'Gene expression correlates of neurofibrillary tangles in Alzheimer's disease', Neurobiology of aging, vol. 27, no. 10, pp. 1359-1371. https://doi.org/10.1016/j.neurobiolaging.2005.08.013

@article{7219fda3ea59468cbcda120eda5af75c,

title = "Gene expression correlates of neurofibrillary tangles in Alzheimer's disease",

abstract = "Neurofibrillary tangles (NFT) constitute one of the cardinal histopathological features of Alzheimer's disease (AD). To explore in vivo molecular processes involved in the development of NFTs, we compared gene expression profiles of NFT-bearing entorhinal cortex neurons from 19 AD patients, adjacent non-NFT-bearing entorhinal cortex neurons from the same patients, and non-NFT-bearing entorhinal cortex neurons from 14 non-demented, histopathologically normal controls (ND). Of the differentially expressed genes, 225 showed progressively increased expression (AD NFT neurons > AD non-NFT neurons > ND non-NFT neurons) or progressively decreased expression (AD NFT neurons < AD non-NFT neurons < ND non-NFT neurons), raising the possibility that they may be related to the early stages of NFT formation. Immunohistochemical studies confirmed that many of the implicated proteins are dysregulated and preferentially localized to NFTs, including apolipoprotein J, interleukin-1 receptor-associated kinase 1, tissue inhibitor of metalloproteinase 3, and casein kinase 2, beta. Functional validation studies are underway to determine which candidate genes may be causally related to NFT neuropathology, thus providing therapeutic targets for the treatment of AD.",

keywords = "Alzheimer's disease, Dementia, Gene expression, Laser capture microdissection, Microarray, NFT, Neurodegeneration, Neurofibrillary tangles",

author = "Travis Dunckley and Beach, {Thomas G.} and Ramsey, {Keri E.} and Andrew Grover and Diego Mastroeni and Walker, {Douglas G.} and LaFleur, {Bonnie J.} and Coon, {Keith D.} and Brown, {Kevin M.} and Richard Caselli and Walter Kukull and Roger Higdon and Daniel McKeel and Morris, {John C.} and Christine Hulette and Donald Schmechel and Reiman, {Eric M.} and Joseph Rogers and Stephan, {Dietrich A.}",

note = "Funding Information: We would like to thank the National Institute on Aging's Alzheimer's Disease Centers program and the National Alzheimer's Coordinating Committee for their invaluable assistance in accessing banked samples. We also thank Zhouwen Liu for assistance with statistical analyses and Phanindra Tangirala and Steven Day for their efforts to make this data publicly available. This study was supported in part by grants from the National Institute on Aging (#1-RO1-AG023193 to DAS; P30 AG19610 to EMR; P50 AG05681 to JCM; P01 AG03991 to JCM; AG05128 for the Duke University ADC), the National Alzheimer's Coordinating Center (U01AG016976), and the Arizona Alzheimer's Research Center (to EMR) under a collaborative agreement from the National Institute on Aging.",

year = "2006",

month = oct,

doi = "10.1016/j.neurobiolaging.2005.08.013",

language = "English (US)",

volume = "27",

pages = "1359--1371",

journal = "Neurobiology of aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

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TY - JOUR

T1 - Gene expression correlates of neurofibrillary tangles in Alzheimer's disease

AU - Dunckley, Travis

AU - Beach, Thomas G.

AU - Ramsey, Keri E.

AU - Grover, Andrew

AU - Mastroeni, Diego

AU - Walker, Douglas G.

AU - LaFleur, Bonnie J.

AU - Coon, Keith D.

AU - Brown, Kevin M.

AU - Caselli, Richard

AU - Kukull, Walter

AU - Higdon, Roger

AU - McKeel, Daniel

AU - Morris, John C.

AU - Hulette, Christine

AU - Schmechel, Donald

AU - Reiman, Eric M.

AU - Rogers, Joseph

AU - Stephan, Dietrich A.

N1 - Funding Information: We would like to thank the National Institute on Aging's Alzheimer's Disease Centers program and the National Alzheimer's Coordinating Committee for their invaluable assistance in accessing banked samples. We also thank Zhouwen Liu for assistance with statistical analyses and Phanindra Tangirala and Steven Day for their efforts to make this data publicly available. This study was supported in part by grants from the National Institute on Aging (#1-RO1-AG023193 to DAS; P30 AG19610 to EMR; P50 AG05681 to JCM; P01 AG03991 to JCM; AG05128 for the Duke University ADC), the National Alzheimer's Coordinating Center (U01AG016976), and the Arizona Alzheimer's Research Center (to EMR) under a collaborative agreement from the National Institute on Aging.

PY - 2006/10

Y1 - 2006/10

N2 - Neurofibrillary tangles (NFT) constitute one of the cardinal histopathological features of Alzheimer's disease (AD). To explore in vivo molecular processes involved in the development of NFTs, we compared gene expression profiles of NFT-bearing entorhinal cortex neurons from 19 AD patients, adjacent non-NFT-bearing entorhinal cortex neurons from the same patients, and non-NFT-bearing entorhinal cortex neurons from 14 non-demented, histopathologically normal controls (ND). Of the differentially expressed genes, 225 showed progressively increased expression (AD NFT neurons > AD non-NFT neurons > ND non-NFT neurons) or progressively decreased expression (AD NFT neurons < AD non-NFT neurons < ND non-NFT neurons), raising the possibility that they may be related to the early stages of NFT formation. Immunohistochemical studies confirmed that many of the implicated proteins are dysregulated and preferentially localized to NFTs, including apolipoprotein J, interleukin-1 receptor-associated kinase 1, tissue inhibitor of metalloproteinase 3, and casein kinase 2, beta. Functional validation studies are underway to determine which candidate genes may be causally related to NFT neuropathology, thus providing therapeutic targets for the treatment of AD.

AB - Neurofibrillary tangles (NFT) constitute one of the cardinal histopathological features of Alzheimer's disease (AD). To explore in vivo molecular processes involved in the development of NFTs, we compared gene expression profiles of NFT-bearing entorhinal cortex neurons from 19 AD patients, adjacent non-NFT-bearing entorhinal cortex neurons from the same patients, and non-NFT-bearing entorhinal cortex neurons from 14 non-demented, histopathologically normal controls (ND). Of the differentially expressed genes, 225 showed progressively increased expression (AD NFT neurons > AD non-NFT neurons > ND non-NFT neurons) or progressively decreased expression (AD NFT neurons < AD non-NFT neurons < ND non-NFT neurons), raising the possibility that they may be related to the early stages of NFT formation. Immunohistochemical studies confirmed that many of the implicated proteins are dysregulated and preferentially localized to NFTs, including apolipoprotein J, interleukin-1 receptor-associated kinase 1, tissue inhibitor of metalloproteinase 3, and casein kinase 2, beta. Functional validation studies are underway to determine which candidate genes may be causally related to NFT neuropathology, thus providing therapeutic targets for the treatment of AD.

KW - Alzheimer's disease

KW - Dementia

KW - Gene expression

KW - Laser capture microdissection

KW - Microarray

KW - NFT

KW - Neurodegeneration

KW - Neurofibrillary tangles

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SN - 0197-4580

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JO - Neurobiology of aging

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Gene expression correlates of neurofibrillary tangles in Alzheimer's disease

Abstract

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