Abstract:
:PICALM, a clathrin adaptor protein, plays important roles in clathrin-mediated endocytosis in all cell types. Recently, genome-wide association studies identified single nucleotide polymorphisms in PICALM gene as genetic risk factors for late-onset Alzheimer disease (LOAD). We analysed by western blotting with several anti-PICALM antibodies the pattern of expression of PICALM in human brain extracts. We found that PICALM was abnormally cleaved in AD samples and that the level of the uncleaved 65-75 kDa full-length PICALM species was significantly decreased in AD brains. Cleavage of human PICALM after activation of endogenous calpain or caspase was demonstrated in vitro. Immunohistochemistry revealed that PICALM was associated in situ with neurofibrillary tangles, co-localising with conformationally abnormal and hyperphosphorylated tau in LOAD, familial AD and Down syndrome cases. PHF-tau proteins co-immunoprecipitated with PICALM. PICALM was highly expressed in microglia in LOAD. These observations suggest that PICALM is associated with the development of AD tau pathology. PICALM cleavage could contribute to endocytic dysfunction in AD.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Ando K,Brion JP,Stygelbout V,Suain V,Authelet M,Dedecker R,Chanut A,Lacor P,Lavaur J,Sazdovitch V,Rogaeva E,Potier MC,Duyckaerts Cdoi
10.1007/s00401-013-1111-zsubject
Has Abstractpub_date
2013-06-01 00:00:00pages
861-78issue
6eissn
0001-6322issn
1432-0533journal_volume
125pub_type
杂志文章abstract::Gelatinase A is an enzyme capable of cleaving soluble beta-amyloid protein (beta AP), and may function as an alpha-secretase to produce secretory forms of amyloid precursor protein. We examined gelatinase A immunoreactivity in the brains and posterior roots of neurologically normal, lacunar stroke, Alzheimer disease (...
journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00293325
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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abstract::This report concerns an immunocytochemical and ultrastructural study of the motor cortices of 11 patients with amyotrophic lateral sclerosis (ALS). Specimens from 12 normal individuals served as controls. Antibodies against phosphorylated neurofilament (PNF; 200 kDa), ubiquitin, glial fibrillary acidic protein (GFAP) ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00293318
更新日期:1994-01-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
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abstract::Long-term epidemiological studies indicate that environmental factors play a causative role in high-incidence amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) in the western Pacific. An increased risk for disease is acquired in youth and remains for life. The low concentrations of calcium and magnesi...
journal_title:Acta neuropathologica
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更新日期:1989-01-01 00:00:00
abstract::Vasa vasorum are adventitial vessels that play a role in pathogenesis of atherosclerosis, aneurysm, vasculitides, and graft vascular disease. The existence of vasa vasorum in human intracranial arteries is not yet well defined. The specific aims of this study are to determine whether the human intracranial arteries ha...
journal_title:Acta neuropathologica
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更新日期:2000-05-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/s00401-014-1305-z
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687981
更新日期:1986-01-01 00:00:00
abstract::The thoracic sympathetic preganglionic outflow is important in the maintenance of postural normotension in man. Normative data on the intermediolateral column (ILC) neuron cell bodies is lacking. Counts and measurements on the right ILC cytons have been performed on the T6, T7 and T8 segments of 12 spinal cords of man...
journal_title:Acta neuropathologica
pub_type: 杂志文章
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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