Dense-core senile plaques in the Flemish variant of Alzheimer's disease are vasocentric

被引:90
作者
Kumar-Singh, S
Cras, P
Wang, R
Kros, JM
van Swieten, J
Lübke, U
Ceuterick, C
Serneels, S
Vennekens, K
Timmermans, JP
Van Marck, E
Martin, JJ
van Duijn, CM
Van Broeckhoven, C
机构
[1] Univ Instelling Antwerp VIB, Dept Mol Genet, B-2610 Antwerp, Belgium
[2] Univ Instelling Antwerp, Born Bunge Fdn, Lab Neurol, B-2610 Antwerp, Belgium
[3] Univ Instelling Antwerp, Born Bunge Fdn, Neuropathol Lab, B-2610 Antwerp, Belgium
[4] Univ Instelling Antwerp, Histol Lab, B-2610 Antwerp, Belgium
[5] Univ Instelling Antwerp, Pathol Lab, B-2610 Antwerp, Belgium
[6] CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA
[7] Univ Rotterdam Hosp, Dept Pathol, Rotterdam, Netherlands
[8] Univ Rotterdam Hosp, Dept Neurol, Rotterdam, Netherlands
[9] Erasmus Univ, Dept Epidemiol & Biostat, NL-3000 DR Rotterdam, Netherlands
关键词
D O I
10.1016/S0002-9440(10)64207-1
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Alzheimer's disease (AD) is characterized by deposition of beta-amyloid (Abeta) in diffuse and senile plaques and variably in vessels. Mutations in the Abeta-encoding region of the amyloid precursor protein (APP) gene are frequently associated with very severe forms of vascular Abeta deposition, sometimes also accompanied by AD pathology. We earlier described a Flemish APP (A692G) mutation causing a form of early-onset AD with a prominent cerebral amyloid angiopathy and unusually large senile plaque cores. The pathogenic basis of Flemish AD is unknown. By image and mass spectrometric Abeta analyses, we demonstrated that in contrast to other familial AD cases with predominant brain Abeta42, Flemish AD patients predominantly deposit Abeta40. On serial histological section analysis we further showed that the neuritic senile plaques in APP692 brains were centered on vessels. Of a total of 2400 senile plaque cores studied from various brain regions from three patients, 68% enclosed a vessel, whereas the remainder were associated with vascular walls. These observations were confirmed by electron microscopy coupled with examination of serial semi-thin plastic sections, as well as three-dimensional observations by confocal microscopy. Diffuse plaques did not associate with vessels, or with neuritic or inflammatory pathology. Together with earlier in vitro data on APP692, our analyses suggest that the altered biological properties of the Flemish APP and Abeta facilitate progressive Abeta deposition in vascular walls that in addition to causing strokes, initiates formation of dense-core senile plaques in the Flemish variant of AD.
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页码:507 / 520
页数:14
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