Abstract
A recent report showed that the accumulation of α-synuclein (α-syn) was detected in the brains of one-third of Alzheimer's disease and Down syndrome patients. However, the relationship between amyloid-β protein (Aβ) and α-syn remains unclear. We analyzed the relation between the mutation of presenilin-1 (PS-1) and the pathological features of β-amyloidosis and α-synucleinopathy. We generated doubly transgenic mice overexpressing mutant β-amyloid precursor protein (βAPP; Tg2576) and mutant PS-1 (PS1L286Vtg; line 198) and analyzed 19 double Tg βAPP +/PS+ mice at 5-23 months (young to old), 23 age-matched single Tg βAPP+/PS- mice, and 11 non-Tg littermates. Immunohistochemical comparison was performed in these three groups by counting the area and the number of α-syn- or phosphorylated α-syn (pα-syn)-positive dystrophic neurites per plaque (ASPDN, pASPDN). The acceleration of Aβ pathology was found with earlier onset and exaggerated numbers in double Tg βAPP+/ PS+ compared with single Tg βAPP+/PS- mouse brains. The accumulation of ASPDN and pASPDN was also accelerated in double Tg βAPP+/PS + compared with single Tg βAPP+/PS- mouse brains, especially in pASPDN. The number and area of α-syn and pα-syn, and the ratio of pα-syn positive neurites were significantly higher in double Tg βAPP+/PS+ than in single Tg βAPP+/PS- mouse brains in middle-aged and old groups. Additional overexpression of mutant PS-1 accelerated Aβ-induced α-synucleinopathy and further facilitated the phosphorylation of α-syn, suggesting a direct association between mutant PS-1 and phosphorylation of α-syn.
| Original language | English |
|---|---|
| Pages (from-to) | 2246-2252 |
| Number of pages | 7 |
| Journal | Journal of Neuroscience Research |
| Volume | 85 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Aug 1 2007 |
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Keywords
- Alzheimer's disease
- Phosphorylation
- Presenilin-1
- Synuclein
- Transgenic mouse
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Enhanced accumulation of phosphorylated α-synuclein in double transgenic mice expressing mutant β-amyloid precursor protein and presenilin-1. / Kurata, Tomoko; Kawarabayashi, Takeshi; Murakami, Tetsuro; Miyazaki, Kazunori; Morimoto, Nobutoshi; Ohta, Yasuyuki; Takehisa, Yasushi; Nagai, Makiko; Ikeda, Masaki; Matsubara, Etsuro; Westaway, David; Hyslop, Peter St George; Harigaya, Yasuo; Kamiya, Tatsushi; Shoji, Mikio; Abe, Koji.
In: Journal of Neuroscience Research, Vol. 85, No. 10, 01.08.2007, p. 2246-2252.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Enhanced accumulation of phosphorylated α-synuclein in double transgenic mice expressing mutant β-amyloid precursor protein and presenilin-1
AU - Kurata, Tomoko
AU - Kawarabayashi, Takeshi
AU - Murakami, Tetsuro
AU - Miyazaki, Kazunori
AU - Morimoto, Nobutoshi
AU - Ohta, Yasuyuki
AU - Takehisa, Yasushi
AU - Nagai, Makiko
AU - Ikeda, Masaki
AU - Matsubara, Etsuro
AU - Westaway, David
AU - Hyslop, Peter St George
AU - Harigaya, Yasuo
AU - Kamiya, Tatsushi
AU - Shoji, Mikio
AU - Abe, Koji
PY - 2007/8/1
Y1 - 2007/8/1
N2 - A recent report showed that the accumulation of α-synuclein (α-syn) was detected in the brains of one-third of Alzheimer's disease and Down syndrome patients. However, the relationship between amyloid-β protein (Aβ) and α-syn remains unclear. We analyzed the relation between the mutation of presenilin-1 (PS-1) and the pathological features of β-amyloidosis and α-synucleinopathy. We generated doubly transgenic mice overexpressing mutant β-amyloid precursor protein (βAPP; Tg2576) and mutant PS-1 (PS1L286Vtg; line 198) and analyzed 19 double Tg βAPP +/PS+ mice at 5-23 months (young to old), 23 age-matched single Tg βAPP+/PS- mice, and 11 non-Tg littermates. Immunohistochemical comparison was performed in these three groups by counting the area and the number of α-syn- or phosphorylated α-syn (pα-syn)-positive dystrophic neurites per plaque (ASPDN, pASPDN). The acceleration of Aβ pathology was found with earlier onset and exaggerated numbers in double Tg βAPP+/ PS+ compared with single Tg βAPP+/PS- mouse brains. The accumulation of ASPDN and pASPDN was also accelerated in double Tg βAPP+/PS + compared with single Tg βAPP+/PS- mouse brains, especially in pASPDN. The number and area of α-syn and pα-syn, and the ratio of pα-syn positive neurites were significantly higher in double Tg βAPP+/PS+ than in single Tg βAPP+/PS- mouse brains in middle-aged and old groups. Additional overexpression of mutant PS-1 accelerated Aβ-induced α-synucleinopathy and further facilitated the phosphorylation of α-syn, suggesting a direct association between mutant PS-1 and phosphorylation of α-syn.
AB - A recent report showed that the accumulation of α-synuclein (α-syn) was detected in the brains of one-third of Alzheimer's disease and Down syndrome patients. However, the relationship between amyloid-β protein (Aβ) and α-syn remains unclear. We analyzed the relation between the mutation of presenilin-1 (PS-1) and the pathological features of β-amyloidosis and α-synucleinopathy. We generated doubly transgenic mice overexpressing mutant β-amyloid precursor protein (βAPP; Tg2576) and mutant PS-1 (PS1L286Vtg; line 198) and analyzed 19 double Tg βAPP +/PS+ mice at 5-23 months (young to old), 23 age-matched single Tg βAPP+/PS- mice, and 11 non-Tg littermates. Immunohistochemical comparison was performed in these three groups by counting the area and the number of α-syn- or phosphorylated α-syn (pα-syn)-positive dystrophic neurites per plaque (ASPDN, pASPDN). The acceleration of Aβ pathology was found with earlier onset and exaggerated numbers in double Tg βAPP+/ PS+ compared with single Tg βAPP+/PS- mouse brains. The accumulation of ASPDN and pASPDN was also accelerated in double Tg βAPP+/PS + compared with single Tg βAPP+/PS- mouse brains, especially in pASPDN. The number and area of α-syn and pα-syn, and the ratio of pα-syn positive neurites were significantly higher in double Tg βAPP+/PS+ than in single Tg βAPP+/PS- mouse brains in middle-aged and old groups. Additional overexpression of mutant PS-1 accelerated Aβ-induced α-synucleinopathy and further facilitated the phosphorylation of α-syn, suggesting a direct association between mutant PS-1 and phosphorylation of α-syn.
KW - Alzheimer's disease
KW - Phosphorylation
KW - Presenilin-1
KW - Synuclein
KW - Transgenic mouse
UR - http://www.scopus.com/inward/record.url?scp=34547483466&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547483466&partnerID=8YFLogxK
U2 - 10.1002/jnr.21352
DO - 10.1002/jnr.21352
M3 - Article
C2 - 17526016
AN - SCOPUS:34547483466
VL - 85
SP - 2246
EP - 2252
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
SN - 0360-4012
IS - 10
ER -