Neuronal and glial β-secretase (BACE) protein expression in transgenic Tg2576 mice with amyloid plaque pathology

Steffen Roßner, Jenny Apelt, Reinhard Schliebs, J. Regino Perez-Polo, Volker Bigl

    Research output: Contribution to journalArticle

    94 Citations (Scopus)

    Abstract

    We measured tissue distribution and expression pattern of the beta-site amyloid precursor protein (APP)-cleaving enzyme (BACE) in the brains of transgenic Tg2576 mice that show amyloid pathology. BACE protein was expressed at high levels in brain; at lower levels in heart and liver; and at very low levels in pancreas, kidney, and thymus and was almost absent in spleen and lung when assayed by Western blot analysis. We observed strictly neuronal expression of BACE protein in the brains of nontransgenic control mice, with the most robust immunocytochemical labeling present in the cerebral cortex, hippocampal formation, thalamus, and cholinergic basal forebrain nuclei. BACE protein levels did not differ significantly between control and transgenic mice or as a result of aging. However, in the aged, 17-month-old Tg2576 mice there was robust amyloid plaque formation, and BACE protein was also present in reactive astrocytes present near amyloid plaques, as shown by double immunofluorescent labeling and confocal laser scanning microscopy. The lack of astrocytic BACE immunoreactivity in young transgenic Tg2576 mice suggests that it is not the APP overexpression but rather the amyloid plaque formation that stimulates astrocytic BACE expression in Tg2576 mice. Our data also suggest that the neuronal overexpression of APP does not induce the overexpression of its metabolizing enzyme in neurons. Alternatively, the age-dependent accumulation of amyloid plaques in the Tg2576 mice does not require increased neuronal expression of BACE. Our data support the hypothesis that neurons are the primary source of β-amyloid peptides in brain and that astrocytic β-amyloid generation may contribute to amyloid plaque formation at later stages or under conditions when astrocytes are activated.

    Original languageEnglish (US)
    Pages (from-to)437-446
    Number of pages10
    JournalJournal of Neuroscience Research
    Volume64
    Issue number5
    DOIs
    StatePublished - Jun 1 2001

    Fingerprint

    Amyloid Precursor Protein Secretases
    Amyloid Plaques
    Neuroglia
    Transgenic Mice
    Pathology
    Amyloid beta-Protein Precursor
    Brain
    Proteins
    Amyloid
    Astrocytes
    Neurons
    Tissue Distribution
    Enzymes
    Basal Ganglia
    Thalamus
    Confocal Microscopy
    Cerebral Cortex
    Thymus Gland
    Cholinergic Agents
    Pancreas

    Keywords

    • β-secretase
    • Aging
    • Alzheimer's disease
    • Amyloid plaques
    • Astrocytes
    • Confocal laser scanning microscopy
    • Gliosis
    • Immunocytochemistry
    • Transgenic mouse brain
    • Western blot analysis

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Neuronal and glial β-secretase (BACE) protein expression in transgenic Tg2576 mice with amyloid plaque pathology. / Roßner, Steffen; Apelt, Jenny; Schliebs, Reinhard; Regino Perez-Polo, J.; Bigl, Volker.

    In: Journal of Neuroscience Research, Vol. 64, No. 5, 01.06.2001, p. 437-446.

    Research output: Contribution to journalArticle

    Roßner, Steffen ; Apelt, Jenny ; Schliebs, Reinhard ; Regino Perez-Polo, J. ; Bigl, Volker. / Neuronal and glial β-secretase (BACE) protein expression in transgenic Tg2576 mice with amyloid plaque pathology. In: Journal of Neuroscience Research. 2001 ; Vol. 64, No. 5. pp. 437-446.
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