Accumulation of Intraneuronal beta-Amyloid 42 Peptides Is Associated with Early Changes in Microtubule-Associated Protein 2 in Neurites and Synapses

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Accumulation of Intraneuronal beta-Amyloid 42 Peptides Is Associated with Early Changes in Microtubule-Associated Protein 2 in Neurites and Synapses. / Takahashi, Reisuke H.; Capetillo-Zarate, Estibaliz; Lin, Michael T.; Milner, Teresa A.; Gouras, Gunnar.

In: PLoS ONE, Vol. 8, No. 1, 2013.

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Takahashi, Reisuke H. ; Capetillo-Zarate, Estibaliz ; Lin, Michael T. ; Milner, Teresa A. ; Gouras, Gunnar. / Accumulation of Intraneuronal beta-Amyloid 42 Peptides Is Associated with Early Changes in Microtubule-Associated Protein 2 in Neurites and Synapses. In: PLoS ONE. 2013 ; Vol. 8, No. 1.

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TY - JOUR

T1 - Accumulation of Intraneuronal beta-Amyloid 42 Peptides Is Associated with Early Changes in Microtubule-Associated Protein 2 in Neurites and Synapses

AU - Takahashi, Reisuke H.

AU - Capetillo-Zarate, Estibaliz

AU - Lin, Michael T.

AU - Milner, Teresa A.

AU - Gouras, Gunnar

PY - 2013

Y1 - 2013

N2 - Pathologic aggregation of beta-amyloid (A beta) peptide and the axonal microtubule-associated protein tau protein are hallmarks of Alzheimer's disease (AD). Evidence supports that A beta peptide accumulation precedes microtubule-related pathology, although the link between A beta and tau remains unclear. We previously provided evidence for early co-localization of A beta 42 peptides and hyperphosphorylated tau within postsynaptic terminals of CA1 dendrites in the hippocampus of AD transgenic mice. Here, we explore the relation between A beta peptide accumulation and the dendritic, microtubule-associated protein 2 (MAP2) in the well-characterized amyloid precursor protein Swedish mutant transgenic mouse (Tg2576). We provide evidence that localized intraneuronal accumulation of A beta 42 peptides is spatially associated with reductions of MAP2 in dendrites and postsynaptic compartments of Tg2576 mice at early ages. Our data support that reduction in MAP2 begins at sites of A beta 42 monomer and low molecular weight oligomer (M/LMW) peptide accumulation. Cumulative evidence suggests that accumulation of M/LMW A beta 42 peptides occurs early, before high molecular weight oligomerization and plaque formation. Since synaptic alteration is the best pathologic correlate of cognitive dysfunction in AD, the spatial association of M/LMW A beta peptide accumulation with pathology of MAP2 within neuronal processes and synaptic compartments early in the disease process reinforces the importance of intraneuronal A beta accumulation in AD pathogenesis.

AB - Pathologic aggregation of beta-amyloid (A beta) peptide and the axonal microtubule-associated protein tau protein are hallmarks of Alzheimer's disease (AD). Evidence supports that A beta peptide accumulation precedes microtubule-related pathology, although the link between A beta and tau remains unclear. We previously provided evidence for early co-localization of A beta 42 peptides and hyperphosphorylated tau within postsynaptic terminals of CA1 dendrites in the hippocampus of AD transgenic mice. Here, we explore the relation between A beta peptide accumulation and the dendritic, microtubule-associated protein 2 (MAP2) in the well-characterized amyloid precursor protein Swedish mutant transgenic mouse (Tg2576). We provide evidence that localized intraneuronal accumulation of A beta 42 peptides is spatially associated with reductions of MAP2 in dendrites and postsynaptic compartments of Tg2576 mice at early ages. Our data support that reduction in MAP2 begins at sites of A beta 42 monomer and low molecular weight oligomer (M/LMW) peptide accumulation. Cumulative evidence suggests that accumulation of M/LMW A beta 42 peptides occurs early, before high molecular weight oligomerization and plaque formation. Since synaptic alteration is the best pathologic correlate of cognitive dysfunction in AD, the spatial association of M/LMW A beta peptide accumulation with pathology of MAP2 within neuronal processes and synaptic compartments early in the disease process reinforces the importance of intraneuronal A beta accumulation in AD pathogenesis.

U2 - 10.1371/journal.pone.0051965

DO - 10.1371/journal.pone.0051965

M3 - Article

VL - 8

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 1

ER -