Distribution of amyloid deposits and senile plaques within the hippocampal and parahippocampal formation of patients with down syndrome

1994 ◽  
Vol 15 ◽  
pp. S112
Keyword(s):  
Down Syndrome ◽  
Senile Plaques ◽  
Amyloid Deposits

Intraneuronal Aβ-Amyloid Precedes Development of Amyloid Plaques in Down Syndrome

2001 ◽  
Vol 125 (4) ◽  
pp. 489-492 ◽  
Author(s):  
Kymberly A. Gyure ◽  
Robert Durham ◽  
Walter F. Stewart ◽  
John E. Smialek ◽  
Juan C. Troncoso
Keyword(s):  
Down Syndrome ◽  
Alzheimer Disease ◽  
Neurofibrillary Tangles ◽  
Senile Plaques ◽  
Medical Examiner ◽  
Johns Hopkins Hospital ◽  
Sequence Of Events ◽  
Amyloid Deposits ◽  
Aβ Amyloid ◽  
Intraneuronal Aβ

Abstract Context.—Down syndrome patients who live to middle age invariably develop the neuropathologic features of Alzheimer disease, providing a unique situation in which to study the early and sequential development of these changes. Objective.—To study the development of amyloid deposits, senile plaques, astrocytic and microglial reactions, and neurofibrillary tangles in the brains of young individuals (<30 years of age) with Down syndrome. Methods.—Histologic and immunocytochemical study of a series of autopsy brains (n = 14, from subjects aged 11 months to 56 years, with 9 subjects <30 years) examined at the Office of the Chief Medical Examiner of the State of Maryland and The Johns Hopkins Hospital. Results.—The principal observations included the presence of intraneuronal Aβ immunostaining in the hippocampus and cerebral cortex of very young Down syndrome patients (preceding the extracellular deposition of Aβ) and the formation of senile plaques and neurofibrillary tangles. Conclusions.—We propose the following sequence of events in the development of neuropathologic changes of Alzheimer disease in Down syndrome: (1) intracellular accumulation of Aβ in neurons and astrocytes, (2) deposition of extracellular Aβ and formation of diffuse plaques, and (3) development of neuritic plaques and neurofibrillary tangles with activation of microglial cells.

scholarly journals Mostly Separate Distributions of CLAC- versus Aβ40- or Thioflavin S-Reactivities in Senile Plaques Reveal Two Distinct Subpopulations of β-Amyloid Deposits

2004 ◽  
Vol 165 (1) ◽  
pp. 273-281 ◽  
Author(s):  
Hisatomo Kowa ◽  
Tomoko Sakakura ◽  
Yusuke Matsuura ◽  
Tomoko Wakabayashi ◽  
David M.A. Mann ◽  
...  
Keyword(s):  
Senile Plaques ◽  
Amyloid Deposits ◽  
Β Amyloid

scholarly journals Colocalization of Apolipoprotein AI in Various Kinds of Systemic Amyloidosis

2005 ◽  
Vol 53 (2) ◽  
pp. 237-242 ◽  
Author(s):  
Naohiro Sakata ◽  
Yoshinobu Hoshii ◽  
Tomomi Nakamura ◽  
Makiko Kiyama ◽  
Hirofumi Arai ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Amyloid Fibrils ◽  
Senile Plaques ◽  
Systemic Amyloidosis ◽  
High Density Lipoproteins ◽  
Apolipoprotein Ai ◽  
Aa Amyloidosis ◽  
Amyloid A ◽  
Amyloid Deposits ◽  
A Minor

Apolipoprotein AI (apoAI), a major component of high-density lipoproteins, is one of the major amyloid fibril proteins and a minor constituent of the senile plaques observed in Alzheimer's disease. We examined colocalization of apoAI in various kinds of systemic amyloidosis in this study. Forty-three of 48 formalin-fixed paraffin-embedded heart specimens with various forms of systemic amyloidosis reacted immunohistochemically with anti-human apoAI antibody. ApoAI was also detected in water-extracted amyloid material by immunoblotting. In addition, we observed colocalization of apoAI and murine amyloid A (AA) amyloidosis in human apoAI transgenic mice. This is the first report of colocalization of apoAI with amyloid deposits in various forms of human systemic amyloidosis and murine AA amyloidosis in human apoAI transgenic mice. ApoAI may not always be a major component of amyloid fibrils, even when it is present in systemic amyloid deposits.

scholarly journals Postmortem Neocortical 3H-PiB Binding and Levels of Unmodified and Pyroglutamate Aβ in Down Syndrome and Sporadic Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Violetta N. Pivtoraiko ◽  
Tamara Racic ◽  
Eric E. Abrahamson ◽  
Victor L. Villemagne ◽  
Benjamin L. Handen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Late Onset ◽  
Amyloid Β ◽  
Molecular Profile ◽  
Amyloid Angiopathy ◽  
Neuritic Plaques ◽  
Amyloid Deposits

Individuals with Down syndrome (DS) have a genetic predisposition for amyloid-β (Aβ) overproduction and earlier onset of Aβ deposits compared to patients with sporadic late-onset Alzheimer’s disease (AD). Positron emission tomography (PET) with Pittsburgh Compound-B (PiB) detects fibrillar Aβ pathology in living people with DS and AD, but its relationship with heterogeneous Aβ forms aggregated within amyloid deposits is not well understood. We performed quantitative in vitro3H-PiB binding assays and enzyme-linked immunosorbent assays of fibrillar (insoluble) unmodified Aβ40 and Aβ42 forms and N-terminus truncated and pyroglutamate-modified AβNpE3-40 and AβNpE3-42 forms in postmortem frontal cortex and precuneus samples from 18 DS cases aged 43–63 years and 17 late-onset AD cases aged 62–99 years. Both diagnostic groups had frequent neocortical neuritic plaques, while the DS group had more severe vascular amyloid pathology (cerebral amyloid angiopathy, CAA). Compared to the AD group, the DS group had higher levels of Aβ40 and AβNpE3-40, while the two groups did not differ by Aβ42 and AβNpE3-42 levels. This resulted in lower ratios of Aβ42/Aβ40 and AβNpE3-42/AβNpE3-40 in the DS group compared to the AD group. Correlations of Aβ42/Aβ40 and AβNpE3-42/AβNpE3-40 ratios with CAA severity were strong in DS cases and weak in AD cases. Pyroglutamate-modified Aβ levels were lower than unmodified Aβ levels in both diagnostic groups, but within group proportions of both pyroglutamate-modified Aβ forms relative to both unmodified Aβ forms were lower in the DS group but not in the AD group. The two diagnostic groups did not differ by 3H-PiB binding levels. These results demonstrate that compared to late-onset AD cases, adult DS individuals with similar severity of neocortical neuritic plaques and greater CAA pathology have a preponderance of both pyroglutamate-modified AβNpE3-40 and unmodified Aβ40 forms. Despite the distinct molecular profile of Aβ forms and greater vascular amyloidosis in DS cases, cortical 3H-PiB binding does not distinguish between diagnostic groups that are at an advanced level of amyloid plaque pathology. This underscores the need for the development of CAA-selective PET radiopharmaceuticals to detect and track the progression of cerebral vascular amyloid deposits in relation to Aβ plaques in individuals with DS.

CHROMOSOME 21q21 SUBLOCALISATION OF GENE ENCODING BETA-AMYLOID PEPTIDE IN CEREBRAL VESSELS AND NEURITIC (SENILE) PLAQUES OF PEOPLE WITH ALZHEIMER DISEASE AND DOWN SYNDROME

The Lancet ◽  
1987 ◽  
Vol 329 (8529) ◽  
pp. 384-385 ◽  
Author(s):  
NikolaosK. Robakis ◽  
HenrykM. Wisniewski ◽  
EdmundC. Jenkins ◽  
EvelynA. Devine-Gage ◽  
GeorgeE. Houck ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Alzheimer Disease ◽  
Senile Plaques ◽  
Beta Amyloid ◽  
Cerebral Vessels ◽  
Amyloid Peptide ◽  
Gene Encoding ◽  
Beta Amyloid Peptide

Molecular Dating of Senile Plaques in the Brains of Individuals with Down Syndrome and in Aged Dogs

2000 ◽  
Vol 163 (1) ◽  
pp. 111-122 ◽  
Author(s):  
Bassem Y. Azizeh ◽  
Elizabeth Head ◽  
Michael A. Ibrahim ◽  
Reidun Torp ◽  
Andrea J. Tenner ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Senile Plaques ◽  
Molecular Dating

scholarly journals The BACH1/Nrf2 Axis in Brain in Down Syndrome and Transition to Alzheimer Disease-Like Neuropathology and Dementia

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 779
Author(s):  
Marzia Perluigi ◽  
Antonella Tramutola ◽  
Sara Pagnotta ◽  
Eugenio Barone ◽  
D. Allan Butterfield
Keyword(s):  
Down Syndrome ◽  
Senile Plaques ◽  
Redox Homeostasis ◽  
Antioxidant Defense System ◽  
Chromosome 21 ◽  
Potential Contribution ◽  
Physiological Relevance ◽  
Increased Risk ◽  
Hyperphosphorylated Tau Protein ◽  
The Brain

Down syndrome (DS) is the most common genetic cause of intellectual disability that is associated with an increased risk to develop early-onset Alzheimer-like dementia (AD). The brain neuropathological features include alteration of redox homeostasis, mitochondrial deficits, inflammation, accumulation of both amyloid beta-peptide oligomers and senile plaques, as well as aggregated hyperphosphorylated tau protein-containing neurofibrillary tangles, among others. It is worth mentioning that some of the triplicated genes encoded are likely to cause increased oxidative stress (OS) conditions that are also associated with reduced cellular responses. Published studies from our laboratories propose that increased oxidative damage occurs early in life in DS population and contributes to age-dependent neurodegeneration. This is the result of damaged, oxidized proteins that belong to degradative systems, antioxidant defense system, neuronal trafficking. and energy metabolism. This review focuses on a key element that regulates redox homeostasis, the transcription factor Nrf2, which is negatively regulated by BACH1, encoded on chromosome 21. The role of the Nrf2/BACH1 axis in DS is under investigation, and the effects of triplicated BACH1 on the transcriptional regulation of Nrf2 are still unknown. In this review, we discuss the physiological relevance of BACH1/Nrf2 signaling in the brain and how the dysfunction of this system affects the redox homeostasis in DS neurons and how this axis may contribute to the transition of DS into DS with AD neuropathology and dementia. Further, some of the evidence collected in AD regarding the potential contribution of BACH1 to neurodegeneration in DS are also discussed.

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