Diminished taxol/GTP-stimulated tubulin polymerization in diseased region of brain from patients with late-onset or inherited Alzheimer's disease or frontotemporal dementia with parkinsonism linked to chromosome-17 but not individuals with mild cognitive impairment

Article type: Research Article

Authors: Boutté, Angela M.^a | Neely, M. Diana^b | Bird, Thomas D.^{c; *} | Montine, Kathleen S.^d | Montine, Thomas J.^d

Affiliations: [a] Center for Molecular Neuroscience Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA | [b] Department of Psychiatry, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA | [c] University of Washington and Department of Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA | [d] Department of Pathology, University of Washington, Harborview Medical Center, Seattle, WA 98104, USA

Correspondence: [*] Corresponding author: Thomas J. Montine, MD, PhD, Department of Pathology, University of Washington, Harborview Medical Center, Box 359791, Seattle, WA 98104, USA. Tel.: +1 206 341 5248; Fax: +1 206 3441 5249; E-mail: [email protected].

Abstract: Neuronal microtubules are morphologically abnormal in diseased regions of brain from patients with late-onset Alzheimer's disease (LOAD). Here we tested the hypothesis that tubulin derived from gray matter of patients with multiple forms of dementia was functionally impaired. Following taxol/GTP stimulation of tubulin polymerization of gray matter extracts we observed reduced capacity of tubulin to polymerize in LOAD, but not individuals with mild cognitive impairment (MCI), compared to controls. Moreover, we observed similarly reduced taxol/GTP-stimulated tubulin polymerization from gray matter obtained from patients with AD caused by PSEN2 N141I mutation or frontotemporal dementia with parkinsonism linked to chromosome-17 caused (FTDP-17) by TAU V337M or P301L mutation. Our results show that modification of tubulin function may contribute to intermediate or late stages in the pathogenesis of sporadic and inherited AD as well as FTDP-17.

Keywords: Alzheimer's disease, presenilin 2, frontotemporal dementia with parkinsonism linked to chromosome-17, mild cognitive impairment, tubulin, microtubules

DOI: 10.3233/JAD-2005-8101

Journal: Journal of Alzheimer's Disease, vol. 8, no. 1, pp. 1-6, 2005