Abstract：
:Aggregation and toxicity of the amyloid β-peptide (Aβ) are considered as critical events in the initiation and progression of Alzheimer's disease (AD). Recent evidence indicated that soluble oligomeric Aβ assemblies exert pronounced toxicity, rather than larger fibrillar aggregates that deposit in the forms of extracellular plaques. While some rare mutations in the Aβ sequence that cause early-onset AD promote the oligomerization, molecular mechanisms that induce the formation or stabilization of oligomers of the wild-type Aβ remain unclear. Here, we identified an Aβ variant phosphorylated at Ser26 residue (pSer26Aβ) in transgenic mouse models of AD and in human brain that shows contrasting spatio-temporal distribution as compared to non-phosphorylated Aβ (npAβ) or other modified Aβ species. pSer26Aβ is particularly abundant in intraneuronal deposits at very early stages of AD, but much less in extracellular plaques. pSer26Aβ assembles into a specific oligomeric form that does not proceed further into larger fibrillar aggregates, and accumulates in characteristic intracellular compartments of granulovacuolar degeneration together with TDP-43 and phosphorylated tau. Importantly, pSer26Aβ oligomers exert increased toxicity in human neurons as compared to other known Aβ species. Thus, pSer26Aβ could represent a critical species in the neurodegeneration during AD pathogenesis.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Kumar S,Wirths O,Stüber K,Wunderlich P,Koch P,Theil S,Rezaei-Ghaleh N,Zweckstetter M,Bayer TA,Brüstle O,Thal DR,Walter Jdoi
10.1007/s00401-016-1546-0subject
Has Abstractpub_date
2016-04-01 00:00:00pages
525-37issue
4eissn
0001-6322issn
1432-0533pii
10.1007/s00401-016-1546-0journal_volume
131pub_type
杂志文章abstract：:Activating beta-catenin mutations with aberrant cytoplasmic and nuclear protein accumulation are hallmarks of adamantinomatous craniopharyngiomas (adaCP). These tumours tend to be associated with unfavourable and occasionally disastrous sequelae, as they invade adjacent brain structures such as the hypothalamus. The p...
journal_title：Acta neuropathologica
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doi：10.1007/s00401-010-0642-9
更新日期：2010-05-01 00:00:00
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journal_title：Acta neuropathologica
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doi：10.1007/s00401-010-0717-7
更新日期：2010-10-01 00:00:00
abstract：:A 9-year-old male patient developed a germ cell tumor in the right basal ganglia which secreted beta-human chorionic gonadotropin (beta-HCG) and caused precocious puberty. Histology and immunohistochemical staining for placental alkaline phosphatase (PLAP), alpha-fetoprotein (alpha-FP), and beta-HCG showed a mixed pop...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687797
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journal_title：Acta neuropathologica
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doi：10.1007/BF00309622
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00308480
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010050559
更新日期：1996-12-01 00:00:00
abstract：:An unusual case of concurrent MS and anaplastic astrocytoma is presented. MS was diagnosed in a female patient at the age of 22 years. A left side thalamotomy was performed for relief of severe intention tremor at age 28 and at age 32 she received immunosuppressive therapy for 1 year. At the age of 36 after a severe e...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00690850
更新日期：1979-05-15 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00703316
更新日期：1977-08-16 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687824
更新日期：1985-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00689558
更新日期：1978-01-19 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00685251
更新日期：1984-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00691427
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00703200
更新日期：1983-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688193
更新日期：1987-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-012-1002-8
更新日期：2012-10-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00690368
更新日期：1981-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00571510
更新日期：1995-01-01 00:00:00
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journal_title：Acta neuropathologica
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更新日期：2017-03-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687775
更新日期：1988-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
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journal_title：Acta neuropathologica
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doi：10.1007/s004010050763
更新日期：1998-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00702677
更新日期：1979-03-15 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
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更新日期：1998-10-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687718
更新日期：1989-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00307635
更新日期：1990-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-009-0544-x
更新日期：2010-01-01 00:00:00
abstract：:Neurotrophins regulate the proliferation and differentiation of neurons in the central nervous system via a family of specialized receptors, including TrkA, TrkB, and TrkC. As little is known about their expression or potential role in human glial tissues and glial tumors, we undertook an immunohistochemical analysis ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010050906
更新日期：1998-10-01 00:00:00
