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Mitochondrial alterations near amyloid plaques in an Alzheimer’s disease mouse model
Open accessAbstract
While accumulation of amyloid-β (Aβ) deposited as senile plaques is a hallmark feature of Alzheimer's disease (AD), the neurotoxicity of these deposits remains controversial. Recent in vitro studies suggested a link between elevated Aβ and mitochondrial dysfunction that might contribute to the pathogenesis of AD. However, the in vivo evidence for mitochondria dysfunction caused by Aβ is still missing. Using intravital multiphoton imaging with a range of fluorescent markers, we systematically surveyed mitochondrial structural and functional changes in AD mouse models. We observed severe impairments to be limited to the vicinity of Aβ plaques, which included reduction of both numbers and membrane potential of mitochondria and the emergence of dystrophic and fragmented mitochondria. Both neuronal soma and neurites with oxidative stress show severe alterations in mitochondrial membrane potential in amyloid precursor protein mice. These results provide in vivo evidence revealing Aβ plaques as focal sources of toxicity that lead to severe structural and functional abnormalities in mitochondria. These alterations may contribute to neuronal network dysfunction and warrant further investigation as possible targets for therapeutic intervention in AD.
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TL;DR
Using intravital multiphoton imaging in APPswe:PSEN1dE9 mice, this study found that mitochondrial structural and functional abnormalities are largely restricted to the immediate vicinity of amyloid plaques. Mitochondria far from plaques appeared mostly normal, whereas near plaques there was mitochondrial loss, fragmentation/swelling, and reduced membrane potential.
Key findings
- Mitochondrial burden was significantly decreased within 16 µm of plaque borders compared with areas far from plaques (n = 13 plaques from 4 animals).
- Mitochondrial swelling was detected near 26 of 109 imaged/analyzed plaques from six animals, while cytosolic GFP-labeled neurites showed dystrophic morphology near all plaques (7 animals). Fragmented mitochondria occurred in 18 neurons from six Tg mice, with lengths of 2–4 µm; fragmented-mitochondria neurons were 38.4 ± 9.2 per mm³ in Tg mice versus 2.1 ± 1.4 per mm³ in Wt mice (n = 6 mice per genotype).
- Far from plaques (>50 µm), mitochondrial function did not differ significantly between Tg and Wt mice: JC-1 red/green ratio was 2.04 ± 0.16 in Wt versus 2.19 ± 0.15 in Tg (n = 12 imaging sites from 3 animals each), and MTR/MTG ratio was 4.03 ± 0.16 in Wt versus 4.35 ± 0.19 in Tg.
- Near plaques, MMP decreased over a ~20 µm radius: JC-1 ratio fell to 83% of the far-from-plaque value (n = 17 plaques from 5 animals); TMRE showed reduced signal near plaques (n = 46 plaques from 3 animals); MTR/MTG ratio decreased near plaques (n = 18 plaques from 4 animals). Dystrophic neurites had lower TMRE signal than normal neurites (0.38 ± 0.02, n = 80 vs 0.97 ± 0.01, n = 82; 5 animals), and oxidized neurons/neurites also showed reduced MMP (oxidized neurons 0.15 ± 0.03, n = 12 vs normal 0.97 ± 0.01, n = 93; oxidized neurites 0.38 ± 0.02, n = 80 vs normal 0.96 ± 0.01, n = 82; 3 animals). CAA did not reduce MMP in smooth muscle cells of leptomeningeal vessels (n ≥ 21 vessels from 5 mice).
Methods
- Intravital multiphoton imaging was performed in living APPswe:PSEN1dE9 transgenic mice (7–10 months old) and age-matched nontransgenic littermate controls, using cranial window implantation and methoxy-XO4 labeling of amyloid plaques.
- Mitochondria were labeled with viral mtGFP (lentivirus and AAV), AAV-GFP, AAV-roGFP, and mitochondrial dyes including MTR, MTG, TMRE, JC-1, DiOC6, and MitoFluo Red 589; FCCP was used to validate MMP-sensitive dyes, and COX IV immunostaining assessed mitochondrial loss.
- Image stacks were processed with ImageJ and IDL; plaque boundaries were defined at half-maximum methoxy-XO4 fluorescence, mitochondrial signal was measured in concentric bands (4 or 6 µm intervals), and data were reported as mean ± SE with t tests.
Limitations
- The paper states that the MTR/MTG ratio might be affected by differential diffusion/penetration rates of the two dyes in tissue, so caution is needed when imaging deep structures.
- The paper notes that lentivirus infects neurons and glial cells, so signal decreases near plaques might reflect mitochondrial loss in both cell types; AAV-mediated neuronal labeling was used to address this.
- Evident from the text: findings are from an AD mouse model and correlational in vivo imaging, not human AD tissue or causal manipulation; the study also does not establish the sequence linking calcium dysregulation, oxidative stress, and mitochondrial abnormalities, which the authors identify as important for future experiments.
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55 Own result · 20 Own interpretation · 11 Own method · 9 Not checked yet · 3 No basis given
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In the paper
“In contrast, cytosolic GFP-labeled neurites showed dramatic swelling/dystrophic morphology near all plaques, which is consistent with previous reports in AD mouse models (Tsai et al., 2004) and AD tissue (Cras et al., 1991; Fig. 1C, bottom, D; 7 animals).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
What the sources say
- Not checked yetcites Tsai et al., 2004
- Not checked yetcites Cras et al., 1991
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“In total, we detected mitochondrial swelling near 26 plaques from six animals, out of a total of 109 plaques that were imaged and analyzed (Fig. 1D).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
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“We observed a similar mitochondrial loss near amyloid plaques in Tg mice (data not shown) using this virus.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
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“No mtGFP signal was observed in the dense-core of A plaques, consistent with our observations that neurites do not traverse through plaques (Spires et al., 2005).”
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“However, a gross reduction of the mtGFP signal was observed around the methoxy-XO4-labeled plaques (Fig. 1B, top), suggesting that dense-core plaques caused a significant loss of mitochondria near the plaque borders.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
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“Furthermore, mtGFP expression revealed mitochondrial swelling in neurites (dendrites or axons) that was observed in the immediate vicinity of a fraction of dense-core plaques (Fig. 1C, top).”
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“The mitochondrial “burden” within the range of 16 m from the boundary of plaques was significantly decreased compared with that in the areas far from the plaques (n ϭ 13 plaques from 4 animals).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
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“In addition to the change in number, mitochondrial morphology was also affected in Tg mouse brain.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
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“Remaining mitochondria near plaques were often fragmented and swollen.”
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“Furthermore, the JC-1 fluorescence ratio (red/green) decreased from 2.48 Ϯ 0.25 in untreated sites to 0.34 Ϯ 0.08 in FCCP-treated sites (n Ն 11 imaging sites from 2 animals, p Ͻ 0.001).”
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“The morphological alterations of mitochondria in those neurons was seldom observed in neurons in agematched Wt mice 2.1 Ϯ 1.4 neurons per mm 3 brain volume, in contrast to 38.4 Ϯ 9.2 neurons per mm 3 in Tg mice (Fig. 2C; Wt, n ϭ 6 mice; Tg, n ϭ 6 mice).”
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“Consistent with the previous data, there was a decrease in ratio that extended to ϳ20 m from the boundary of plaques (Fig. 4A; n ϭ 17 plaques from 5 animals).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
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“Both neuronal soma and neurites with oxidative stress show severe alterations in mitochondrial membrane potential in amyloid precursor protein mice.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Abstract
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“Moreover, mitochondria within ϳ20 m from plaques exhibited significant reductions in MMP, suggesting that amyloid plaques play a role as a source of toxicity that affects mitochondria function.”
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“The range of decreased MMP revealed by TMRE also extended to ϳ20 m from the boundary of plaques (Fig. 4B; n ϭ 46 plaques from 3 animals).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
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“The ratio of MTR/MTG was not changed in Tg mice compared with Wt controls (Fig. 3D; Wt ϭ 4.03 Ϯ 0.16, n ϭ 60 imaging sites from 3 animals; Tg ϭ 4.35 Ϯ 0.19, n ϭ 65 imaging sites from 4 animals).”
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“In wild-type (Wt) mouse brain, the mitochondrial cable-like structures in neurons were typically 2-30 m long (Fig. 2B).”
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“Punctate TMRE staining was present in GFPlabeled dystrophic neurites (Fig. 5 B, C) near a subset of plaques, suggesting that there are some functional mitochondria remaining in the dystrophic neurites.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
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“Together, we observed a dramatic decrease in mitochondrial numbers in areas adjacent to A plaques.”
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“None of the tested dyes loaded brain with this approach (data not shown).”
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“Thus, no significant difference was observed in mitochondrial function between Wt and Tg mice.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
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“Near plaques, there is a reduced density of mitochondria, abnormal morphology of mitochondria, and a loss of mitochondrial membrane potential in remaining mitochondria.”
- Also stated in: § Discussion · boosted
“There is a dramatic reduction in mitochondrial signal in the vicinity of dense-core plaques in APP/PS1 transgenic mice.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
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“Surprisingly, in Tg mice, although the morphology of mitochondria in most of the neurons (Ͼ97% observed neurons in six Tg mice) appear to be normal, a small number of neurons close to plaques displayed fragmented mitochondria (18 neurons in six Tg mice; Fig. 2A, bottom).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
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“Detection of oxidized cell bodies is an extremely rare event.”
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“Similar to the observation in cultured neurons, mtGFP-labeled mitochondria showed cable-like structures in living mouse brain (Fig. 2A, top).”
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“Compared with normal neurons without oxidative stress (Fig. 6A, yellow cells), MMP indicated by TMRE staining was significantly decreased in oxidized neurons (green cell, 0.15 Ϯ 0.03 in oxidized neurons, n ϭ 12, vs 0.97 Ϯ 0.01 in normal neurons, n ϭ 93; 3 animals; values are normalized fluorescent ratios of individual neurites vs average fluorescence intensity within each imaging plane; Fig. 6 A,”
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“Similar decreases were observed with TMRE staining, a commonly used dye that results in MMPsensitive loading of mitochondria (Fig. 4B), confirming a deficit in mitochondria function that is associated with plaques.”
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“We consistently observed a decrease of COX subunit IV staining associated with plaques (Fig. 1E), which suggested the loss of intact mitochondria surrounding plaques.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
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“Together, these data demonstrate that mitochondrial number was significantly decreased in the areas immediately adjacent to plaques.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
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“More detailed analysis showed that the TMRE intensity in dystrophic neurites was widely distributed, in contrast with those in normal neurites which showed a much tighter distribution.”
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“We showed that the majority of mitochondria in the brains of mice with amyloid plaques appear structurally and functionally normal.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
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“Severe alterations in MMP were also observed in oxidized neurites (0.38 Ϯ 0.02 in oxidized neurites, n ϭ 80, vs 0.96 Ϯ 0.01 in normal neurites, n ϭ 82; 3 animals; values are normalized fluorescent ratios of individual neurites vs average fluorescence intensity within each imaging plane; Fig. 6 B, C).”
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“The ratio of MTR to MTG fluorescence was decreased from 4.05 Ϯ 0.43 to 0.70 Ϯ 0.16 (n Ն 8 imaging sites from 2 animals, p Ͻ 0.001; Fig. 3A).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
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“Near plaques, there is a reduced density of mitochondria, abnormal morphology of mitochondria, and a loss of mitochondrial membrane potential in remaining mitochondria.”
- Also stated in: § Discussion · plain
“The bottom images show a neuron near plaques in a Tg mouse brain that shows severe fragmentation of mitochondria as a result of excessive mitochondrial fission.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
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“In this area, the average JC-1 fluorescent ratio (red/green) was significantly decreased to 83% of the value far from plaques (Fig. 4A), indicating a reduction of MMP of individual mitochondria near plaques.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
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“Severe alterations in mitochondria structure and function were, however, detected, but only in the proximity of dense core plaques.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
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“In contrast to the toxicity of amyloid deposits in neuronal tissues, we were unable to detect a decrease in mitochondrial function (MMP) in smooth muscle cells of leptomeningeal vessels near amyloid deposits, as indicated by TMRE staining (Fig. 4D).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
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“In close proximity to senile plaques, we observed decreased mitochondrial numbers stained with the functional dyes, consistent with our previous results.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Surprisingly, in Tg mice, although the morphology of mitochondria in most of the neurons (Ͼ97% observed neurons in six Tg mice) appear to be normal, a small number of neurons close to plaques displayed fragmented mitochondria (18 neurons in six Tg mice; Fig. 2A, bottom).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
hedgedn = 6- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The JC-1 red/green ratio was 2.04 Ϯ 0.16 (n ϭ 12 imaging sites from 3 animals) in Wt controls and 2.19 Ϯ 0.15 in Tg mice (n ϭ 12 imaging sites from 3 animals).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
plainn = 3- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Oxidative stress was accompanied by mitochondrial dysfunction in living APP/PS1 transgenic mouse.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
plaincorrelationaln = 3- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The robust deficits occur within a halo that surrounds individual plaques, resulting in a ϳ20 m radius of toxicity.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Together, these in vivo observations, for the first time, revealed mitochondrial impairments in AD mouse models.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
boosted- Asserted: passes — The authors put it forward as true.
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In the paper
“Summary data that indicate that compared with normal neurites, the TMRE fluorescence in the dystrophic neurites was dramatically decreased and widely distributed (n ϭ 5 animal, p Ͻ 0.001).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
hedgedcorrelationaln = 5- Asserted: passes — The authors put it forward as true.
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In the paper
“More dystrophic neurites than swollen mitochondria were observed near plaques in Tg mice.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Immunofluorescence of COX IV (red) showing loss of COX IV surrounding plaques.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“CAA does not affect mitochondrial function in smooth muscle cells.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Dystrophic neurites show severe alterations in MMP as shown in these representative images.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
plaincorrelationaln = 5- Asserted: passes — The authors put it forward as true.
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In the paper
“Both neuronal soma and neurites with oxidative stress show severe alterations in MMP as shown in these representative images.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
plaincorrelationaln = 3- Asserted: passes — The authors put it forward as true.
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In the paper
“Near plaques, there is a reduced density of mitochondria, abnormal morphology of mitochondria, and a loss of mitochondrial membrane potential in remaining mitochondria.”
- Also stated in: § Discussion · plain
“The MMP-sensitive JC-1 ratio was decreased near plaques.”
- Also stated in: § Discussion · boosted
“A loss in membrane potential is confirmed using the fluorescent dye TMRE that shows a reduced signal near plaques in Tg mice.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
boostedcorrelationaln = 46- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MMP was not altered in areas far from amyloid plaques in the APP/PS1 transgenic mice.”
- Also stated in: § Discussion · boosted
“No differences in the JC-1 ratio were observed in areas distant to A plaques (Ͼ50 m) in Tg mouse, compared with Wt mouse, demonstrating that most mitochondria have a normal resting membrane potential.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
boostedn = 5- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Discussion · boosted
In the paper
“No mtGFP signal was observed in the dense-core of A plaques, consistent with our observations that neurites do not traverse through plaques (Spires et al., 2005).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
What the sources say
- Not checked yetcites Spires et al., 2005
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, a gross reduction of the mtGFP signal was observed around the methoxy-XO4-labeled plaques (Fig. 1B, top), suggesting that dense-core plaques caused a significant loss of mitochondria near the plaque borders.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
hedgeddirectn = 4- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results suggest that the soluble aggregates of A in the Tg mice do not lead to appreciable changes in mitochondrial function and morphology in areas far from A plaques.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
hedgedn = 3- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, mitochondria within ϳ20 m from plaques exhibited significant reductions in MMP, suggesting that amyloid plaques play a role as a source of toxicity that affects mitochondria function.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results provide in vivo evidence revealing A plaques as focal sources of toxicity that lead to severe structural and functional abnormalities in mitochondria.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, we validated approaches for studying mitochondrial function in vivo via topical application of TMRE, DiOC 6 , and JC-1, as well as MTR and MTG.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
plainn = 2 ·- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Punctate TMRE staining was present in GFPlabeled dystrophic neurites (Fig. 5 B, C) near a subset of plaques, suggesting that there are some functional mitochondria remaining in the dystrophic neurites.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
hedged- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, there is a larger variance in mitochondrial function and numbers in dystrophic neurites near plaques (Fig. 5C).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
plaincorrelationaln = 5- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“JC-1 staining in living mouse brain exhibited mitochondrial localization as expected (Fig. 3B).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results are also consistent with the morphological studies with mtGFP virus labeling (Fig. 1) demonstrating that the majority of the mitochondria are not affected in the Tg mice.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
boostedn = 4- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This result demonstrates that the MMP in dystrophic neurites was reduced.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
boosteddirectn = 5- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results demonstrate that mitochondrial function is severely impaired in the dystrophic neurites near amyloid plaques.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
boosteddirectn = 5- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, the efforts to associate A toxicity with mitochondrial dysfunction are still limited to in vitro studies.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed a significant reduction of both MTR signal and MTG signal, indicating loss of mitochondria in the immediate vicinity of plaques (Fig. 4C).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
hedgeddirectn = 4- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this area, the average JC-1 fluorescent ratio (red/green) was significantly decreased to 83% of the value far from plaques (Fig. 4A), indicating a reduction of MMP of individual mitochondria near plaques.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
hedgeddirectn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This observation suggests that CAA does not have a direct effect on mitochondrial function in vessels with moderate vascular amyloid deposition.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
hedged- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We consistently observed a decrease of COX subunit IV staining associated with plaques (Fig. 1E), which suggested the loss of intact mitochondria surrounding plaques.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similar decreases were observed with TMRE staining, a commonly used dye that results in MMPsensitive loading of mitochondria (Fig. 4B), confirming a deficit in mitochondria function that is associated with plaques.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
plaincorrelationaln = 4- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“AAVmediated GFP expression in cortical neurons did not change the MMP indicated by TMRE staining (0.99 Ϯ 0.02 in GFP-negative neurons, n ϭ 23, vs 0.95 Ϯ 0.02 in GFP-positive neurons, n ϭ 26; 3 animals; values are normalized fluorescent ratios of individual neurites vs average fluorescence intensity within each imaging plane; Fig. 5A).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
plainn = 3- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, the ratio of MTR and MTG fluorescence could be used as a ratiometric indicator of mitochondrial function.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
hedgedcorrelationaln = 2- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“When applied directly to the neocortex of anesthetized mice, most of the dyes showed mitochondria-like localization (Figs.3A, MTG, MTR; B, JC-1, Fig. 4 B, TMRE).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Right insert indicates that no significant change of MMP induced by AAV-mediated GFP expression (n ϭ 5 animal, p Ͻ 0.001).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
hedgedn = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“FCCP reduced the MMP in vivo as indicated with the MTR/MTG signal ratio in Wt mouse cortex.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
hedgeddirectn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The probe is based on ratiometric imaging of fluorescence excited at 800 nm (oxidized) and 900 nm (reduced) and can be used as an index of the redox status of roGFP.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
What the sources say
- Not checked yetcites Dooley et al., 2004
- Not checked yetcites Cannon and Remington, 2008
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results demonstrate a direct connection between mitochondrial dysfunction and amyloid plaques.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, our previous reports examining calcium dyshomeostasis and the current results that correlate oxidative stress with mitochondrial dysfunction suggest that these pathways may be mechanistically linked.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“This halo corresponds well with previous reports demonstrating local alterations in spine density, neuritic curvature, calcium dysregulation, and oxidative stress (Spires et al., 2005;Kuchibhotla et al., 2008;Meyer-Luehmann et al., 2008;Koffie et al., 2009;Xie et al., 2013).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
What the sources say
- Not checked yetcites Spires et al., 2005
- Not checked yetcites Kuchibhotla et al., 2008
- Not checked yetcites Meyer-Luehmann et al., 2008
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“FCCP reduced the MMP in vivo as indicated with the JC-1 ratio (red/green) in Wt mouse cortex.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
hedgeddirectn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 14
- Probably not a substantial claim. 9
- The quote only partly states this claim. 1
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed a significant reduction of both MTR signal and MTG signal, indicating loss of mitochondria in the immediate vicinity of plaques (Fig. 4C).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
hedgedcorrelationaln = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed severe impairments to be limited to the vicinity of A plaques, which included reduction of both numbers and membrane potential of mitochondria and the emergence of dystrophic and fragmented mitochondria.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among the six dyes, the MitoFluo Red 589 signal was very weak and photobleached rapidly, and thus was not pursued further.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The lengths of fragmented mitochondria were distributed from 2 to 4 m (Fig. 2B).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, the ratio of MTR/MTG in remaining mitochondria decreased dramatically near plaques.The MMP decrease extended to ϳ20 m from the border of plaques (Fig. 4C; n ϭ 18 plaques from 4 animals).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
plaincorrelationaln = 18- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The fluorescence signal of MTR was reduced in the FCCP-treated side compared with the untreated side while the MTG signal was unaffected (Fig. 3A).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
plaindirectn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In the transgenic (Tg) mice (APPswe:PSEN1dE9), the levels of A increase with age and A plaques are observed at ϳ4 months of age, accumulating progressively afterward (Garcia-Alloza et al., 2006).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
What the sources say
- Not checked yetcites Garcia-Alloza et al., 2006
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The discrepancy between these studies may be related to the much higher concentrations of synthetic A generally used in in vitro studies, or there exist compensatory mechanisms in the intact brain to accommodate diffuse low level neurotoxic insults.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A variety of in vitro investigations have revealed that mitochondria have reduced membrane potential, increased permeability, increased ROS production, altered trafficking, and aberrant fission/fusion regulation when exposed to A (Keller et al., 1997;Mattson et al., 1998; Abramov et al., 2004;Lustbader et al., 2004;Manczak et al., 2006;Wang et al., 2008;Reddy, 2009;Calkins et al., 2011;Manczak et”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
What the sources say
- Not checked yetcites Keller et al., 1997 source
- Not checked yetcites Mattson et al., 1998
- Not checked yetcites Abramov et al., 2004
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Using a similar approach, we also verified that both TMRE and DiOC 6 exhibited fluorescence changes in response to FCCP treatment (data not shown) in in situ assays.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“To consolidate the evidence for A-induced mitochondrial dysfunction in AD pathogenesis, the alterations in mitochondrial morphology and function in living animals remains to be elucidated.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“By exploiting this reporter, we have previously determined that oxidative stress was most dramatic in neurites near plaques, propagated to cell bodies, and preceded activation of caspases that led to cell death within 24 h (Xie et al., 2013).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
What the sources say
- Not checked yetcites Xie et al., 2013
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“When tested in cultured CHO cells, all dyes showed mitochondriaspecific staining (data not shown), as previously described”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“However, it should be noted that the ratio might also be affected by a differential diffusion/penetration rate of the two dyes in tissues, so caution must be used when imaging deep structures.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This surprising result is in stark contrast to the numerous reports using in vitro models that demonstrate more global disruption in response to exogenous A.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Thus, consistent with previous reports in cultured cells and isolated mouse lens (Pendergrass et al., 2004), MTR can be used as a functional mitochondrial marker and MTG can be used as a structural mitochondrial marker.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
What the sources say
- Not checked yetcites Pendergrass et al., 2004
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Deficiency of COX has been reported in dystrophic neurites of senile plaques (Pe ´rez-Gracia et al., 2008).”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
What the sources say
- Not checked yetcites Pe ´rez-Gracia et al., 2008
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nonetheless, as the number of senile plaques increases with age, the amount and severity of neuropathological alterations will also increase, leading to progressive neural network dysfunction.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This reduction in MMP is a surrogate to impaired energy production by mitochondria, which would have profound implications for local metabolism and activity.”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The APPswe:PSEN1dE9 mouse model is a valid model for studying A plaque-associated mitochondrial alterations in Alzheimer's disease.
“Transgenic mice (7 to 10 months old) of either sex expressing mutant human APPswe/human PS1-⌬E9 were used along with age-matched nontransgenic littermate controls (Borchelt et al., 1997).”
The paper relies on this without support.
FCCP collapses mitochondrial membrane potential.
“To collapse the mitochondrial membrane potential, carbonyl cyanide 4-[trifluoromethoxy] phenylhydrazone (FCCP, 10 M; Sigma) was applied to the left hemisphere before MTR and MTG loading.”
The paper relies on this without support.
There is limited evidence examining the role of mitochondria in vivo, particularly in the presence of classical AD pathology such as senile plaques.
“While these results, as well as investigations in postmortem human tissue, have built a strong case for mitochondrial dysfunction in AD, there is limited evidence examining the role of mitochondria in vivo, particularly in the presence of classical AD pathology, e.g., senile plaques.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Excessive Ca2+ accumulation into mitochondria leads to decreased mitochondrial membrane potential and increased ROS production in the same AD mouse model [67,68,70].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [70]
Experimental — accuracy not yet measuredIn the citing paper
“Aβ can be toxic on neuronal mitochondria and causes Ca2+ elevation, changes in mitochondrial size and shape in APP/PS1 AD mouse model [70].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [70]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
“AAVmediated GFP expression in cortical neurons did not change the MMP indicated by TMRE staining (0.99 Ϯ 0.02 in GFP-negative neurons, n ϭ 23, vs 0.95 Ϯ 0.02 in GFP-positive neurons, n ϭ 26; 3 animals;”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
“Right insert indicates that no significant change of MMP induced by AAV-mediated GFP expression (n ϭ 5 animal, p Ͻ 0.001).”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Results
“0.38 Ϯ 0.02 in oxidized neurites, n ϭ 80, vs 0.96 Ϯ 0.01 in normal neurites, n ϭ 82; 3 animals;”
§ Neurobiology of Disease Mitochondrial Alterations near Amyloid Plaques in an Alzheimer's Disease Mouse Model > Discussion
“n ϭ 8 oxidized neurites from 3 animals, p Ͻ 0.001”
Citations
Cites
Gauthier, S. G., Reisberg, ., Zaudig, M., Petersen, R. C., Ritchie, K. A., Broich, K., Belleville, S., Brodaty, H., Bennett, D. A., Chertkow, H. M., et al. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68542-5 · Cited by 4,094
Mitochondria: Dynamic Organelles in Disease, Aging, and Development
Chan, D. C. (2006) · Cell · doi:10.1016/j.cell.2006.06.010 · Cited by 1,987
Ankarcrona, M., Dypbukt, J. M., Bonfoco, E., Zhivotovsky, B., Orrenius, S., Lipton, S. A., & Nicotera, P. (1995) · Neuron · doi:10.1016/0896-6273(95)90186-8 · Cited by 1,884
Mitochondrial abnormalities in Alzheimer's disease
Hirai, K., Aliev, G., Nunomura, A., Fujioka, H., Russell, R. L., Atwood, C. S., Johnson, A. B., Kress, Y., Vinters, H. V., Tabaton, M., et al. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-09-03017.2001 · Cited by 1,367 · cited 2×
“, 2006) and altered mitochondrial structure has been observed (Hirai et al., 2001; Moreira et al., 2007).”
BackgroundABAD Directly Links Aß to Mitochondrial Toxicity in Alzheimer's Disease
Lustbader, J. W., Cirilli, M., Lin, C., Xu, H. W., Takuma, K., Wang, N., Caspersen, C., Chen, X., Pollak, S., Chaney, M., et al. (2004) · Science · doi:10.1126/science.1091230 · Cited by 1,303
Mitochondrial Membrane Potential Probes and the Proton Gradient: A Practical Usage Guide
Perry, S. W., Norman, J. P., Barbieri, J., Brown, E. B., & Gelbard, H. A. (2011) · BioTechniques · doi:10.2144/000113610 · Cited by 1,196 · cited 1×
“Fluorescent probes for monitoring MMP have been frequently used for assessing mitochondrial function (Johnson et al., 1981; Perry et al., 2011; Nicholls, 2012).”
MethodManczak, M., Anekonda, T. S., Henson, E., Park, B. S., Quinn, J., & Reddy, P. H. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl066 · Cited by 1,104 · cited 3×
“…increased ROS production, altered trafficking, and aberrant fission/fusion regulation when exposed to A (Keller et al., 1997; Mattson et al., 1998; Abramov et al., 2004; Lustbader et al., 2004; Manczak et al., 2006; Wang et al., 2008; Reddy, 2009; Calkins et al., 2011; Manczak et al., 2011).”
BackgroundMitochondria in neuroplasticity and neurological disorders
Mattson, M. P., Gleichmann, M., & Cheng, A. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.010 · Cited by 1,081
Reers, M., Smith, T. W., & Chen, L. B. (1991) · Biochemistry · doi:10.1021/bi00232a015 · Cited by 1,054 · cited 1×
“JC-1 is another vital functional mitochondrial dye used in vitro (Reers et al., 1991; Ankarcrona et al., 1995).”
BackgroundBorchelt, D. R., Ratovitski, T., van Lare, J., Lee, M. K., Gonzales, V., Jenkins, N. A., Copeland, N. G., Price, D. L., & Sisodia, S. S. (1997) · Neuron · doi:10.1016/s0896-6273(00)80974-5 · Cited by 1,023
Cited by
Sorted by citations
Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: Recent advances.
Wang, W., Zhao, F., Ma, X., Perry, G., & Zhu, X. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00376-6 · Cited by 1,274
Molecular mechanisms and consequences of mitochondrial permeability transition
Bonora, M., Giorgi, C., & Pinton, P. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00433-y · Cited by 578
Kamat, P. K., Kalani, A., Rai, S., Swarnkar, S., Tota, S., Nath, C., & Tyagi, N. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-9053-6 · Cited by 511
“Inhibition of caspase-3 activity is beneficial to reverse cognitive decline in APP mice possibly due to a requirement for caspase-3 activity in normal synaptic function [37, 38].”
Synaptic degeneration in Alzheimer disease
Tzioras, M., McGeachan, R. I., Durrant, C. S., & Spires-Jones, T. L. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-022-00749-z · Cited by 504
Amyloid toxicity in Alzheimer’s disease
Reiss, A. B., Arain, H. A., Stecker, M. M., Siegart, N. M., & Kasselman, L. J. (2018) · Reviews in the Neurosciences · doi:10.1515/revneuro-2017-0063 · Cited by 447
Metadata
- Authors
- Xie, H., Guan, J., Borrelli, L. A., Xu, J., Serrano-Pozo, A., & Bacskai, B. J.
- Affiliations
- Massachusetts General Hospital (US)
- Tsinghua University (CN)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-10-23
- Volume
- 33
- Issue
- 43
- Pages
- 17042-17051
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3807029
- OpenAlex
- W2035815961
- Semantic Scholar
- 56c270d0938a0df939e932a219eaa2a69bb16728
- Cited by
- 185
- References
- 49
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 11 · 2023: 12 · 2022: 18 · 2021: 23 · 2020: 14 · 2019: 8 · 2018: 19 · 2017: 9 · 2016: 18 · 2015: 16 · 2014: 17 · 2013: 2
- FWCI
- 12.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (2011Z02143, NCSF31100776)
- National Institute on Aging (AG024688, R01AG024688)
- National Institute of Biomedical Imaging and Bioengineering (EB 000768, R01EB000768)
- National Center for Research Resources (S10RR025645)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid plaques, mitochondrial dysfunction, mitochondrial membrane potential, mitochondrial fragmentation, oxidative stress, neurites, neurotoxicity
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Mice, Transgenic, Mitochondria, Neurites, Amyloid beta-Protein Precursor, Oxidative Stress, Mice, Membrane Potential, Mitochondrial, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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