Early Aβ accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain

M. Ingelsson, H. Fukumoto, K. L. Newell, J. H. Growdon, E. T. Hedley-Whyte, M. P. Frosch, Marilyn Albert, B. T. Hyman, M. C. Irizarry

Research output: Contribution to journalArticle

Abstract

Background: Pathologic changes in the Alzheimer disease (AD) brain occur in a hierarchical neuroanatomical pattern affecting cortical, subcortical, and limbic regions. Objective: To define the time course of pathologic and biochemical changes-amyloid deposition, amyloid β-peptide (Aβ) accumulation, neurofibrillary tangle (NFT) formation, synaptic loss, and gliosis-within the temporal association cortex of AD cases of varying disease duration, relative to control brains. Methods: Stereologic assessments of amyloid burden and tangle density as well as ELISA-based measurements of Aβ, synaptophysin, and glial fibrillary acidic protein (GFAP) were performed in the superior temporal sulcus from a cohort of 83 AD and 26 nondemented control brains. Results: Relative to control cases, AD brains were characterized by accumulation of NFT and amyloid plaques, increase of tris- and formic acid-extractable Aβ species, reduced levels of synaptophysin, and elevated levels of GFAP. In AD cases, the duration of dementia correlated with the degree of tangle formation, gliosis, and synaptic loss but not with any Aβ measures. Accumulation of Aβ, measured both neuropathologically and biochemically, was markedly increased in AD brains independent of disease duration, even in cases of short duration. Conclusions: These data support distinct processes in the initiation and progression of AD pathology within the temporal cortex: Deposition of Aβ reaches a "ceiling" early in the disease process, whereas NFT formation, synaptic loss, and gliosis continue throughout the course of the illness.

Original languageEnglish (US)
Pages (from-to)925-931
Number of pages7
JournalNeurology
Volume62
Issue number6
StatePublished - Mar 23 2004
Externally publishedYes

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Gliosis
Alzheimer Disease
Brain
Neurofibrillary Tangles
Temporal Lobe
Amyloid
Synaptophysin
formic acid
Glial Fibrillary Acidic Protein
Amyloid Plaques
Brain Diseases
Dementia
Enzyme-Linked Immunosorbent Assay
Pathology

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ingelsson, M., Fukumoto, H., Newell, K. L., Growdon, J. H., Hedley-Whyte, E. T., Frosch, M. P., ... Irizarry, M. C. (2004). Early Aβ accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain. Neurology, 62(6), 925-931.

Early Aβ accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain. / Ingelsson, M.; Fukumoto, H.; Newell, K. L.; Growdon, J. H.; Hedley-Whyte, E. T.; Frosch, M. P.; Albert, Marilyn; Hyman, B. T.; Irizarry, M. C.

In: Neurology, Vol. 62, No. 6, 23.03.2004, p. 925-931.

Research output: Contribution to journalArticle

Ingelsson, M, Fukumoto, H, Newell, KL, Growdon, JH, Hedley-Whyte, ET, Frosch, MP, Albert, M, Hyman, BT & Irizarry, MC 2004, 'Early Aβ accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain', Neurology, vol. 62, no. 6, pp. 925-931.
Ingelsson M, Fukumoto H, Newell KL, Growdon JH, Hedley-Whyte ET, Frosch MP et al. Early Aβ accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain. Neurology. 2004 Mar 23;62(6):925-931.
Ingelsson, M. ; Fukumoto, H. ; Newell, K. L. ; Growdon, J. H. ; Hedley-Whyte, E. T. ; Frosch, M. P. ; Albert, Marilyn ; Hyman, B. T. ; Irizarry, M. C. / Early Aβ accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain. In: Neurology. 2004 ; Vol. 62, No. 6. pp. 925-931.
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AU - Hedley-Whyte, E. T.

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