The DOI matches its Crossref record; 152 of the 157 references it cites were found in a registry or an index; 19 of the 220 sources its claims cite were checked for support.
Brain aging, Alzheimer's disease, and mitochondria
Open accessAbstract
The relationship between brain aging and Alzheimer’s disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the question of whether AD and brain aging should be conceptually lumped or split, the extent to which AD and brain aging potentially share common molecular mechanisms, whether beta amyloid should be primarily considered a marker of AD or simply brain aging, and the definition of AD itself.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review argues that Alzheimer’s disease (AD) and brain aging may be mechanistically linked, with mitochondrial dysfunction as a possible upstream driver of late-onset AD and beta amyloid (Aβ) as a downstream marker. It contrasts this mitochondrial cascade hypothesis with the amyloid cascade hypothesis and notes that new AD criteria classify many elderly individuals with Aβ changes as having preclinical or prodromal AD.
Key findings
- AD is strongly age-associated: it affects 5.4 million Americans and is estimated to cost $385 billion per year; about 1 in 8 people over 65 is estimated to have AD, 40–50% past age 85 may have it, and some very elderly subgroups surpass 50%.
- Aβ pathology is common in non-demented elderly: Pittsburgh Compound B PET studies report roughly 20–40% of non-demented elderly are PIB-positive, rising with age, and 65% of those past 80 show PIB retention; plaques and tangles also occur in non-demented individuals.
- Mitochondrial changes occur in both brain aging and AD: aging shows reduced complex I and complex IV activity with preserved complex II, a 5-kilobase mtDNA deletion increases with age, and mtDNA mutates at approximately 10 times the rate of nuclear DNA; AD shows reduced COX activity in brain, platelets, and fibroblasts, including MCI platelets and young adult APOE4 carriers.
- The mitochondrial cascade hypothesis proposes that age-related mitochondrial decline promotes brain aging features including Aβ accumulation; when mitochondrial decline surpasses a threshold, compensatory mechanisms fail and late-onset AD ensues, making Aβ a downstream marker rather than an upstream cause.
Methods
- Narrative review; no primary data, systematic search, or meta-analysis is described.
- Synthesizes clinical, neuropathological, neuroimaging, biomarker, and mitochondrial/biochemical literature to compare AD and brain aging.
- Discusses evidence from prior cohorts and models, including PIB PET studies, cybrid cell lines, COX activity measurements, and APP-processing experiments.
Limitations
- Stated: descriptive and observational studies cannot assign causality, and mechanistic inferences from descriptive observation are described as frequently inaccurate or misleading; biomarker correlation or chronology does not show that one biomarker change drives another.
- Stated: the mitochondrial cascade hypothesis is a hypothesis and does not address whether Aβ functions as a toxic intermediate in late-onset, non-autosomal dominant AD; it also implies early-onset autosomal dominant and late-onset AD may not share a common etiology.
- Evident from the text: as a narrative review, it provides no new experimental data and relies on selected cited literature and speculative synthesis rather than a systematic assessment.
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Claims the paper makes
72 Not checked yet · 20 Own interpretation · 5 Supported so far · 4 No basis given · 2 Supported · 2 Partly supported · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“In brains from cognitively intact subjects, hippocampal CA1 neuron counts do not correlate with age [47–49].”
§ Brain aging, Alzheimer's disease, and mitochondria > 3. Alzheimer’s Disease Versus Brain Aging: Pathology Perspective
What the sources say
- Not checked yetcites [47] West MJ Coleman PD Flood DG Troncoso JC Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease Lancet 1994 344 769 772 7916070 source
- Supportedcites [48] West MJ Kawas CH Stewart WF Rudow GL Troncoso JC Hippocampal neurons in pre-clinical Alzheimer's disease Neurobiol Aging 2004 25 1205 1212 15312966 source
The Introduction states that CA1 neuron degeneration was disease-specific and not related to aging, based on the authors’ previous study. The Subjects section identifies the controls as cognitively intact, making the claim a fair paraphrase of the age-related finding reported in this paper; the present study does not itself report an age-correlation test. (LLM, conf=0.88)
- Not checked yetcites [49] Imhof A Kovari E von Gunten A Gold G Rivara CB Herrmann FR Hof PR Bouras C Giannakopoulos P Morphological substrates of cognitive decline in nonagenarians and centenarians: a new paradigm? J Neurol Sci 2007 257 72 79 17303173 source
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Whether Aβ changes precede either age-related or AD-related brain bioenergetic changes is less clear-cut, especially since abundant data from human and cell-based studies either suggest or demonstrate bioenergetic factors regulate both APP processing and Aβ production [95–100].”
§ Brain aging, Alzheimer's disease, and mitochondria > 4) Brain Aging and the New Alzheimer’s Disease Diagnostic Criteria
What the sources say
- Not checked yetcites [95] Gabuzda D Busciglio J Chen LB Matsudaira P Yankner BA Inhibition of energy metabolism alters the processing of amyloid precursor protein and induces a potentially amyloidogenic derivative J Biol Chem 1994 269 13623 13628 8175797 source
- Not checked yetcites [96] Gasparini L Racchi M Benussi L Curti D Binetti G Bianchetti A Trabucchi M Govoni S Effect of energy shortage and oxidative stress on amyloid precursor protein metabolism in COS cells Neurosci Lett 1997 231 113 117 9291153 source
- Not checked yetcites [97] Khan SM Cassarino DS Abramova NN Keeney PM Borland MK Trimmer PA Krebs CT Bennett JC Parks JK Swerdlow RH Parker WD Jr Bennett JP Jr Alzheimer's disease cybrids replicate beta-amyloid abnormalities through cell death pathways Ann Neurol 2000 48 148 155 10939564 source
- Not checked yetcites [98] Webster MT Pearce BR Bowen DM Francis PT The effects of perturbed energy metabolism on the processing of amyloid precursor protein in PC12 cells J Neural Transm 1998 105 839 853 9869322 source
- Not checked yetcites [99] Vlassenko AG Vaishnavi SN Couture L Sacco D Shannon BJ Mach RH Morris JC Raichle ME Mintun MA Spatial correlation between brain aerobic glycolysis and amyloid-beta (Abeta) deposition Proc Natl Acad Sci U S A 2010 107 17763 17767 20837517 PMC2955133 source
- Could not verifycites [100] Kang JE Lim MM Bateman RJ Lee JJ Smyth LP Cirrito JR Fujiki N Nishino S Holtzman DM Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle Science 2009 326 1005 1007 19779148 PMC2789838 sourceExperimental — accuracy not yet measured
The passages on sleep–wake behavior and orexin (section labeled Abstract; page unavailable) describe changes in Aβ levels and plaque deposition, not brain bioenergetics. Searches for bioenergetic factors, APP processing, and whether Aβ changes precede age-related or AD-related bioenergetic changes found no passage addressing those points. (LLM, conf=0.74)
hedged- 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 cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Studies of non-demented elderly cohorts overall report approximately 20–40% are PIB-positive [67, 68, 71–78].”
§ Brain aging, Alzheimer's disease, and mitochondria > 3. Alzheimer’s Disease Versus Brain Aging: Pathology Perspective
What the sources say
- Not checked yetcites [67] Rowe CC Ellis KA Rimajova M Bourgeat P Pike KE Jones G Fripp J Tochon-Danguy H Morandeau L O'Keefe G Price R Raniga P Robins P Acosta O Lenzo N Szoeke C Salvado O Head R Martins R Masters CL Ames D Villemagne VL Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging Neurobiol Aging 2010 31 1275 1283 20472326 source
- Supportedcites [68] Jack CR Jr Lowe VJ Weigand SD Wiste HJ Senjem ML Knopman DS Shiung MM Gunter JL Boeve BF Kemp BJ Weiner M Petersen RC Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease Brain 2009 132 1355 1365 19339253 PMC2677798 source
The Results section (Baseline PIB and MRI findings by clinical group and source of subjects) reports that 6 of 21 cognitively normal subjects (29%) were PIB-positive, within the claimed 20–40% range. The Discussion (Longitudinal imaging findings) describes the subjects as generally in their 60s through 80s. This paper supports the cited range for its cognitively normal elderly group, rather than establishing a pooled estimate across studies. (LLM, conf=0.92)
- Supportedcites [71] Aizenstein HJ Nebes RD Saxton JA Price JC Mathis CA Tsopelas ND Ziolko SK James JA Snitz BE Houck PR Bi W Cohen AD Lopresti BJ DeKosky ST Halligan EM Klunk WE Frequent amyloid deposition without significant cognitive impairment among the elderly Arch Neurol 2008 65 1509 1517 19001171 PMC2636844 source
The Results section reports that 9 of 43 elderly control subjects (21%) were amyloid-positive. The Comment section also describes this estimate as similar to findings from earlier amyloid-imaging studies. This paper therefore supports the cited sentence as one study reporting a rate within the approximate 20–40% range. (LLM, conf=0.91)
- Supportedcites [72] Pike KE Savage G Villemagne VL Ng S Moss SA Maruff P Mathis CA Klunk WE Masters CL Rowe CC Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease Brain 2007 130 2837 2844 17928318 source
The β-Amyloid burden section reports that 22% of healthy-aging participants were PIB-positive, within the cited 20–40% range. This paper therefore supports the range as one of the studies cited, rather than establishing an estimate across studies on its own. (LLM, conf=0.88)
- Not checked yetcites [73] Rowe CC Ng S Ackermann U Gong SJ Pike K Savage G Cowie TF Dickinson KL Maruff P Darby D Smith C Woodward M Merory J Tochon-Danguy H O'Keefe G Klunk WE Mathis CA Price JC Masters CL Villemagne VL Imaging beta-amyloid burden in aging and dementia Neurology 2007 68 1718 1725 17502554 source
- Supportedcites [74] Morris JC Roe CM Grant EA Head D Storandt M Goate AM Fagan AM Holtzman DM Mintun MA Pittsburgh compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease Arch Neurol 2009 66 1469 1475 20008650 PMC2798814 source
The Discussion reports PIB positivity in 30% of cognitively normal adults aged 80–88 and says other studies found about 20% in nondemented older adults. Those figures support the citing sentence’s approximate range for elderly cohorts. (LLM, conf=0.88)
- Not checked yetcites [75] Rentz DM Becker JA Moran EK Sardinha M Manning LN T.M. S Mathis CM DeKosky ST Klunk WE Sperling RA Fischman AJ Johnson KA Amyloid imaging with Pittsburgh Compound-B (PIB) in AD, MCI, and highly intelligent older adults Neurology 2006 66 A66
- Partly supportedcites [76] Jack CR Jr Knopman DS Jagust WJ Shaw LM Aisen PS Weiner MW Petersen RC Trojanowski JQ Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade Lancet Neurol 2010 9 119 128 20083042 PMC2819840 sourceExperimental — accuracy not yet measured
In “Biomarker abnormalities precede clinical symptoms” (page not provided), the paper reports that approximately 20–40% of cognitively normal elderly people have evidence of significant amyloid deposition. That figure covers evidence from either amyloid imaging or CSF Aβ42, not specifically the proportion who are PiB-positive; cognitively normal is also narrower than non-demented. (LLM, conf=0.86)
- Partly supportedcites [77] Sperling RA Aisen PS Beckett LA Bennett DA Craft S Fagan AM Iwatsubo T Jack CR Jr Kaye J Montine TJ Park DC Reiman EM Rowe CC Siemers E Stern Y Yaffe K Carrillo MC Thies B Morrison-Bogorad M Wagster MV Phelps CH Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease Alzheimers Dement 2011 7 280 292 21514248 PMC3220946 sourceExperimental — accuracy not yet measured
Section 6 reports that approximately 20–40% of clinically normal older individuals are amyloid-positive, based on both CSF assays and PET amyloid imaging studies. It does not assign that range specifically to PIB-positive individuals; the proportion also varies with cohort age and genetic background. (LLM, conf=0.84)
- Not checked yetcites [78] Mintun MA Larossa GN Sheline YI Dence CS Lee SY Mach RH Klunk WE Mathis CA DeKosky ST Morris JC [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease Neurology 2006 67 446 452 16894106 source
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 sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“According to the mitochondrial cascade hypothesis, mitochondrial function constitutes the crucial link between brain aging and AD.”
§ Brain aging, Alzheimer's disease, and mitochondria > 7) Reconciling Brain Aging and Alzheimer’s Disease: The Mitochondrial Cascade Hypothesis
What the sources say
- Not checked yetcites [123] Swerdlow RH Mitochondria and cell bioenergetics: Increasingly recognized components and a possible etiologic cause of Alzheimer’s disease Antioxid Redox Signal 2011 in press PMC3329949 21902597
- Supportedcites [146] Swerdlow RH Burns JM Khan SM The Alzheimer's disease mitochondrial cascade hypothesis J Alzheimers Dis 2010 20 Suppl 2 S265 S279 20442494 PMC2883665 source
The Core assumptions section says age-related mitochondrial decline, together with a person’s mitochondrial starting point, determines when clinical disease develops. The Conclusions section says the hypothesis reconciles brain-aging and AD research. This supports the claim as a description of the hypothesis, particularly for sporadic, late-onset AD. (LLM, conf=0.93)
- Not checked yetcites [147] Swerdlow RH Khan SM A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease Med Hypotheses 2004 63 8 20 15193340 source
- Supportedcites [148] Swerdlow RH Khan SM The Alzheimer's disease mitochondrial cascade hypothesis: an update Exp Neurol 2009 218 308 315 19416677 PMC2710413 source
The section ‘What is the Mitochondrial Cascade Hypothesis of Sporadic AD?’ says age-related mitochondrial changes push function past a threshold that produces AD-characteristic pathology. ‘Considerations and Implications’ likewise describes declining mitochondrial function as the primary underlying problem connecting aging and sporadic AD. The hypothesis is specifically framed around sporadic AD. (LLM, conf=0.91)
plainstates a cause- 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.
- The authors state this as an assumption: Brain aging and Alzheimer’s disease are mechanistically related.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“It deviates from the amyloid cascade hypothesis by predicting age-related changes in mitochondrial function, rather than mutations or polymorphisms in APP or Aβ processing genes, primarily account for age-associated brain Aβ changes.”
§ Brain aging, Alzheimer's disease, and mitochondria > 7) Reconciling Brain Aging and Alzheimer’s Disease: The Mitochondrial Cascade Hypothesis
What the sources say
- Not checked yetcites [123] Swerdlow RH Mitochondria and cell bioenergetics: Increasingly recognized components and a possible etiologic cause of Alzheimer’s disease Antioxid Redox Signal 2011 in press PMC3329949 21902597
- Supportedcites [146] Swerdlow RH Burns JM Khan SM The Alzheimer's disease mitochondrial cascade hypothesis J Alzheimers Dis 2010 20 Suppl 2 S265 S279 20442494 PMC2883665 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked yetcites [147] Swerdlow RH Khan SM A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease Med Hypotheses 2004 63 8 20 15193340 source
- Supportedcites [148] Swerdlow RH Khan SM The Alzheimer's disease mitochondrial cascade hypothesis: an update Exp Neurol 2009 218 308 315 19416677 PMC2710413 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plainstates a cause- 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.
- The authors state this as an assumption: Brain aging and Alzheimer’s disease are mechanistically related.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Models based on early-onset, autosomal dominant AD may therefore provide limited insight into late-onset, non-autosomal dominant AD.”
§ Brain aging, Alzheimer's disease, and mitochondria > 7) Reconciling Brain Aging and Alzheimer’s Disease: The Mitochondrial Cascade Hypothesis
What the sources say
- Not checked yetcites [123] Swerdlow RH Mitochondria and cell bioenergetics: Increasingly recognized components and a possible etiologic cause of Alzheimer’s disease Antioxid Redox Signal 2011 in press PMC3329949 21902597
- Supportedcites [146] Swerdlow RH Burns JM Khan SM The Alzheimer's disease mitochondrial cascade hypothesis J Alzheimers Dis 2010 20 Suppl 2 S265 S279 20442494 PMC2883665 source
In “Clinical contributions to the hypothesis” (page unavailable), the paper cautions that shared plaques and tangles do not establish a common etiology for young adults with autosomal-dominant family histories and elderly patients. In “Genes determine baseline mitochondrial function and durability” (page unavailable), it distinguishes late-onset, usually non-Mendelian AD from autosomal-dominant AD. Together, these passages support the cautious claim that models of the latter may offer limited insight into the former. (LLM, conf=0.88)
- Not checked yetcites [147] Swerdlow RH Khan SM A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease Med Hypotheses 2004 63 8 20 15193340 source
- Supportedcites [148] Swerdlow RH Khan SM The Alzheimer's disease mitochondrial cascade hypothesis: an update Exp Neurol 2009 218 308 315 19416677 PMC2710413 source
In “Considerations and Implications” (page not available), the paper says treatments effective in autosomal dominant AD could be ineffective in sporadic AD and notes that interventions benefiting APP transgenic mice have not benefited sporadic AD patients. It also identifies modeling sporadic disease as a critical question. These passages support the qualified claim that models based on autosomal dominant AD may offer limited insight into sporadic AD. (LLM, conf=0.90)
hedgedstates a possible cause- 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.
- The authors state this as an assumption: Brain aging and Alzheimer’s disease are mechanistically related.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“In contrast to the amyloid cascade hypothesis, which views Aβ as the primary upstream AD biomarker, the mitochondrial cascade hypothesis in general sees Aβ more as a downstream biomarker of brain aging.”
§ Brain aging, Alzheimer's disease, and mitochondria > 8) Conclusions
What the sources say
- Not checked yetcites [123] Swerdlow RH Mitochondria and cell bioenergetics: Increasingly recognized components and a possible etiologic cause of Alzheimer’s disease Antioxid Redox Signal 2011 in press PMC3329949 21902597
- Supportedcites [146] Swerdlow RH Burns JM Khan SM The Alzheimer's disease mitochondrial cascade hypothesis J Alzheimers Dis 2010 20 Suppl 2 S265 S279 20442494 PMC2883665 source
The Therapeutic Implications section explicitly says the mitochondrial cascade hypothesis sees Aβ accumulation as a downstream event, not the primary problem. The Core Assumptions section links that event to age-related mitochondrial decline, supporting the paraphrase about brain aging. The paper frames this hypothesis chiefly around sporadic, late-onset AD. (LLM, conf=0.88)
- Not checked yetcites [147] Swerdlow RH Khan SM A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease Med Hypotheses 2004 63 8 20 15193340 source
- Supportedcites [148] Swerdlow RH Khan SM The Alzheimer's disease mitochondrial cascade hypothesis: an update Exp Neurol 2009 218 308 315 19416677 PMC2710413 source
In “Is Amyloidosis in Sporadic AD a Primary Event?”, the paper calls Aβ a downstream product of mitochondrial decline in sporadic AD. “Considerations and Implications” describes Aβ plaque accumulation as a common, though not obligatory, consequence of aging. The paper distinguishes autosomal dominant AD, in which Aβ overproduction can be the primary cause of mitochondrial dysfunction. (LLM, conf=0.92)
plainstates a cause- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Frequently, however, alternative pathologies are also seen in demented patients with plaques and tangles [50–52].”
§ Brain aging, Alzheimer's disease, and mitochondria > 3. Alzheimer’s Disease Versus Brain Aging: Pathology Perspective
What the sources say
- Not checked yetcites [50] White L Gelber R Ross W Masaki K Uyehara-Lock JH Launer L Petrovitch H Dissonance in diagnoses of dementia type during life with attribution determined at autopsy in the Honolulu-Asia Aging Study; Impact of high prevalence of mixed pathology and specificity/non-specificity of clinical manifestations in the very old Neurology 2011 PL01.002
- Not checked yetcites [51] Savva GM Wharton SB Ince PG Forster G Matthews FE Brayne C Age, neuropathology, and dementia N Engl J Med 2009 360 2302 2309 19474427 source
- Not checked yetcites [52] Schneider JA Arvanitakis Z Bang W Bennett DA Mixed brain pathologies account for most dementia cases in community-dwelling older persons Neurology 2007 69 2197 2204 17568013 source
plainstates an association- 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.
In the paper
“Brains from AD subjects have fewer CA1 neurons than control subjects [47].”
§ Brain aging, Alzheimer's disease, and mitochondria > 3. Alzheimer’s Disease Versus Brain Aging: Pathology Perspective
What the sources say
- Not checked yetcites [47] West MJ Coleman PD Flood DG Troncoso JC Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease Lancet 1994 344 769 772 7916070 source
plainstates an association- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, the simple presence of plaques and tangles do not distinguish demented from non-demented individuals because brains of non-demented individuals frequently contain plaques and tangles.”
§ Brain aging, Alzheimer's disease, and mitochondria > 3. Alzheimer’s Disease Versus Brain Aging: Pathology Perspective
What the sources say
- Not checked yetcites [53] Hof PR Glannakopoulos P Bouras C The neuropathological changes associated with normal brain aging Histol Histopathol 1996 11 1075 1088 8930649
- Not checked yetcites [54] Arriagada PV Marzloff K Hyman BT Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer's disease Neurology 1992 42 1681 1688 1307688 source
- Not checked yetcites [55] Price JL Morris JC Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease Ann Neurol 1999 45 358 368 10072051 source
- Not checked yetcites [56] Duyckaerts C Hauw JJ Prevalence, incidence and duration of Braak's stages in the general population: can we know? Neurobiol Aging 1997 18 362 369 discussion 389-392 9380250 source
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.
- It may state two separate claims as one. 36
- Probably not a substantial claim. 14
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“According to the new AD diagnostic criteria cognitive decline and an absence of alternative dementia-associated pathology are no longer required features. At least for research purposes, to qualify for a diagnosis of AD altered brain or CSF Aβ is now the sole requirement [77].”
§ Brain aging, Alzheimer's disease, and mitochondria > 4) Brain Aging and the New Alzheimer’s Disease Diagnostic Criteria
What the sources say
- Partly supportedcites [77] Sperling RA Aisen PS Beckett LA Bennett DA Craft S Fagan AM Iwatsubo T Jack CR Jr Kaye J Montine TJ Park DC Reiman EM Rowe CC Siemers E Stern Y Yaffe K Carrillo MC Thies B Morrison-Bogorad M Wagster MV Phelps CH Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease Alzheimers Dement 2011 7 280 292 21514248 PMC3220946 sourceExperimental — accuracy not yet measured
Section 9.1 (page unavailable) proposes a research stage of preclinical AD with PET or CSF evidence of Aβ accumulation and no detectable cognitive symptoms, supporting the point that cognitive decline is not required for that stage. It does not establish Aβ as the sole requirement for a general AD diagnosis or say that alternative dementia-associated pathology need not be considered; section 9 describes a draft framework for staging preclinical AD. (LLM, conf=0.85)
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.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In addition to using Aβ phenomena to distinguish AD from “normal” brain aging, the new criteria make one critical mechanistic assumption. Aβ is identified as an “upstream” AD biomarker [77]. Other biomarkers, including increased CSF tau, CSF phospho-tau, and decreased glucose utilization (as demonstrated by fluorodeoxyglucose PET; FDG PET), are identified as “downstream” biomarkers.”
§ Brain aging, Alzheimer's disease, and mitochondria > 4) Brain Aging and the New Alzheimer’s Disease Diagnostic Criteria
What the sources say
- Supportedcites [77] Sperling RA Aisen PS Beckett LA Bennett DA Craft S Fagan AM Iwatsubo T Jack CR Jr Kaye J Montine TJ Park DC Reiman EM Rowe CC Siemers E Stern Y Yaffe K Carrillo MC Thies B Morrison-Bogorad M Wagster MV Phelps CH Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease Alzheimers Dement 2011 7 280 292 21514248 PMC3220946 source
Section 4 describes Aβ accumulation as an “upstream” marker in the proposed disease model. Section 9.2 explicitly calls elevated CSF tau or phospho-tau and FDG-PET hypometabolism markers of “downstream” neuronal injury. The paper presents this sequence as a model, not a proven causal mechanism, consistent with the claim’s description of it as an assumption. (LLM, conf=0.94)
plainstates a cause- 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. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Soluble interstitial Aβ levels fall in the setting of trauma-induced coma, and rising levels signal clinical recovery [137].”
§ Brain aging, Alzheimer's disease, and mitochondria > 6) Mitochondria and Alzheimer’s Disease
What the sources say
- Supportedcites [137] Brody DL Magnoni S Schwetye KE Spinner ML Esparza TJ Stocchetti N Zipfel GJ Holtzman DM Amyloid-beta dynamics correlate with neurological status in the injured human brain Science 2008 321 1221 1224 18755980 PMC2577829 source
The Abstract reports that brain interstitial-fluid Aβ concentrations fell when neurological status declined and rose as patients improved. The Glasgow Coma Score analysis also found this correlation in traumatic brain injury patients. The paper supports the claim as an observed association, not a prediction of recovery. (LLM, conf=0.90)
plainstates a cause- 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.
- Supported
None of the sources cited for this claim have been checked yet.
In the paper
“Over time, cognitive decline in those with AAMI and AACD tends to progress, the line from no dementia to dementia is frequently crossed, and AD is often diagnosed [3, 22–31].”
§ Brain aging, Alzheimer's disease, and mitochondria > 2. Alzheimer’s Disease Versus Brain Aging: Clinical Perspective
What the sources say
- Not checked yetcites [3] Swerdlow RH Is aging part of Alzheimer's disease, or is Alzheimer's disease part of aging? Neurobiol Aging 2007 28 1465 1480 16876913
- Not checked yetcites [22] Goldman WP Morris JC Evidence that age-associated memory impairment is not a normal variant of aging Alzheimer Dis Assoc Disord 2001 15 72 79 11403335
- Not checked yetcites [23] Backman L Jones S Berger AK Laukka EJ Small BJ Cognitive impairment in preclinical Alzheimer's disease: a meta-analysis Neuropsychology 2005 19 520 531 16060827
- Not checked yetcites [24] Elias MF Beiser A Wolf PA Au R White RF D'Agostino RB The preclinical phase of alzheimer disease: A 22-year prospective study of the Framingham Cohort Arch Neurol 2000 57 808 813 10867777 source
- Not checked yetcites [25] Jacobs DM Sano M Dooneief G Marder K Bell KL Stern Y Neuropsychological detection and characterization of preclinical Alzheimer's disease Neurology 1995 45 957 962 7746414 source
- Not checked yetcites [26] Masur DM Sliwinski M Lipton RB Blau AD Crystal HA Neuropsychological prediction of dementia and the absence of dementia in healthy elderly persons Neurology 1994 44 1427 1432 8058143 source
- Not checked yetcites [27] Morris JC Storandt M Miller JP McKeel DW Price JL Rubin EH Berg L Mild cognitive impairment represents early-stage Alzheimer disease Arch Neurol 2001 58 397 405 11255443
- Not checked yetcites [28] Sacuiu S Sjogren M Johansson B Gustafson D Skoog I Prodromal cognitive signs of dementia in 85-year-olds using four sources of information Neurology 2005 65 1894 1900 16380609
- Not checked yetcites [29] Saxton J Lopez OL Ratcliff G Dulberg C Fried LP Carlson MC Newman AB Kuller L Preclinical Alzheimer disease: neuropsychological test performance 1.5 to 8 years prior to onset Neurology 2004 63 2341 2347 15623697 source
- Not checked yetcites [30] Small BJ Fratiglioni L Viitanen M Winblad B Backman L The course of cognitive impairment in preclinical Alzheimer disease: three- and 6-year follow-up of a population-based sample Arch Neurol 2000 57 839 844 10867781 source
plainstates a cause- 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
“Memory encoding, working memory (a component of executive function), and processing speed all decline with age. Although this decline probably proceeds throughout adulthood it truly becomes evident after the age of 60. Semantic knowledge and autobiographical memory, on the other hand, tend to remain intact.”
§ Brain aging, Alzheimer's disease, and mitochondria > 2. Alzheimer’s Disease Versus Brain Aging: Clinical Perspective
What the sources say
- Not checked yetcites [15] Hedden T Gabrieli JD Insights into the ageing mind: a view from cognitive neuroscience Nat Rev Neurosci 2004 5 87 96 14735112 source
- Not checked yetcites [16] Borson S Cognition, aging, and disabilities: conceptual issues Phys Med Rehabil Clin N Am 2010 21 375 382 20494283 PMC2876094 source
- Not checked yetcites [17] Folstein M Folstein S Functional expressions of the aging brain Nutr Rev 2010 68 Suppl 2 S70 S73 21091951 source
- Not checked yetcites [18] Salthouse TA Memory aging from 18 to 80 Alzheimer Dis Assoc Disord 2003 17 162 167 14512830
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“These neuroimaging studies show advancing age and prefrontal cortical atrophy positively correlate, while hippocampal volumes change to a lesser extent.”
§ Brain aging, Alzheimer's disease, and mitochondria > 2. Alzheimer’s Disease Versus Brain Aging: Clinical Perspective
What the sources say
- Not checked yetcites [15] Hedden T Gabrieli JD Insights into the ageing mind: a view from cognitive neuroscience Nat Rev Neurosci 2004 5 87 96 14735112 source
plainstates an association- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Tau phosphorylation, an event believed to precede tangle formation, is actually found in the temporal lobe transentorhinal region of young adults and with advancing age tau phosphorylation anatomically spreads to include additional regions [57].”
§ Brain aging, Alzheimer's disease, and mitochondria > 3. Alzheimer’s Disease Versus Brain Aging: Pathology Perspective
What the sources say
- Not checked yetcites [57] Braak H Braak E Staging of Alzheimer's disease-related neurofibrillary changes Neurobiol Aging 1995 16 271 278 discussion 278-284 7566337
plainstates an association- 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
“Electron transport chain function declines, while free radical production increases.”
§ Brain aging, Alzheimer's disease, and mitochondria > 5) Mitochondria and the Aging Brain
What the sources say
- Not checked yetcites [106] Lenaz G D'Aurelio M Merlo Pich M Genova ML Ventura B Bovina C Formiggini G Parenti Castelli G Mitochondrial bioenergetics in aging Biochim Biophys Acta 2000 1459 397 404 11004456 source
- Not checked yetcites [107] Navarro A Boveris A The mitochondrial energy transduction system and the aging process Am J Physiol Cell Physiol 2007 292 C670 C686 17020935 source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“When analyzed according to age, though, the percentage of non-demented subjects who are PIB-positive increases with advancing age and the majority of those past 80 years of age (65%) show PIB retention [67].”
§ Brain aging, Alzheimer's disease, and mitochondria > 3. Alzheimer’s Disease Versus Brain Aging: Pathology Perspective
What the sources say
- Not checked yetcites [67] Rowe CC Ellis KA Rimajova M Bourgeat P Pike KE Jones G Fripp J Tochon-Danguy H Morandeau L O'Keefe G Price R Raniga P Robins P Acosta O Lenzo N Szoeke C Salvado O Head R Martins R Masters CL Ames D Villemagne VL Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging Neurobiol Aging 2010 31 1275 1283 20472326 source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Exemplifying this is a report of a 115 year-old supercentenarian (a term applied to individuals beyond 110 years of age) who did not clinically dement during life and whose brain, on autopsy, showed very limited tau pathology and almost no fibrillar Aβ deposition [82].”
§ Brain aging, Alzheimer's disease, and mitochondria > 4) Brain Aging and the New Alzheimer’s Disease Diagnostic Criteria
What the sources say
- Not checked yetcites [82] den Dunnen WF Brouwer WH Bijlard E Kamphuis J van Linschoten K Eggens-Meijer E Holstege G No disease in the brain of a 115-year-old woman Neurobiol Aging 2008 29 1127 1132 18534718 source
plainSingle case- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Several studies report mitochondrial DNA (mtDNA) mutation can initiate aging, or at least accelerate the progression of age-associated phenotypes [108, 109].”
§ Brain aging, Alzheimer's disease, and mitochondria > 5) Mitochondria and the Aging Brain
What the sources say
- Not checked yetcites [108] Trifunovic A Wredenberg A Falkenberg M Spelbrink JN Rovio AT Bruder CE Bohlooly YM Gidlof S Oldfors A Wibom R Tornell J Jacobs HT Larsson NG Premature ageing in mice expressing defective mitochondrial DNA polymerase Nature 2004 429 417 423 15164064 source
- Not checked yetcites [109] Kujoth GC Hiona A Pugh TD Someya S Panzer K Wohlgemuth SE Hofer T Seo AY Sullivan R Jobling WA Morrow JD Van Remmen H Sedivy JM Yamasoba T Tanokura M Weindruch R Leeuwenburgh C Prolla TA Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging Science 2005 309 481 484 16020738 source
plainstates a possible cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mitochondrial mass, or at least parameters related to it, also appear to change during brain aging. Studies are limited, but overall suggest that with advancing age mitochondrial mass increases or attempts to increase.”
§ Brain aging, Alzheimer's disease, and mitochondria > 5) Mitochondria and the Aging Brain
What the sources say
- Not checked yetcites [116] Barrientos A Casademont J Cardellach F Estivill X Urbano-Marquez A Nunes V Reduced steady-state levels of mitochondrial RNA and increased mitochondrial DNA amount in human brain with aging Brain Res Mol Brain Res 1997 52 284 289 9495550 source
- Not checked yetcites [111] Hirai K Aliev G Nunomura A Fujioka H Russell RL Atwood CS Johnson AB Kress Y Vinters HV Tabaton M Shimohama S Cash AD Siedlak SL Harris PL Jones PK Petersen RB Perry G Smith MA Mitochondrial abnormalities in Alzheimer's disease J Neurosci 2001 21 3017 3023 11312286 PMC6762571 source
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Oxidative stress markers also increase in the aging brain. This manifests in the form of protein carbonylation, lipid oxidation, and mtDNA oxidation [117].”
§ Brain aging, Alzheimer's disease, and mitochondria > 5) Mitochondria and the Aging Brain
What the sources say
- Not checked yetcites [117] Boveris A Navarro A Brain mitochondrial dysfunction in aging IUBMB Life 2008 60 308 314 18421773 source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Young adult APOE4 carriers, who also have an increased AD risk, have lower posterior cingulate COX activities than young adult non-APOE4 carriers [133].”
§ Brain aging, Alzheimer's disease, and mitochondria > 6) Mitochondria and Alzheimer’s Disease
What the sources say
- Not checked yetcites [133] Valla J Yaari R Wolf AB Kusne Y Beach TG Roher AE Corneveaux JJ Huentelman MJ Caselli RJ Reiman EM Reduced posterior cingulate mitochondrial activity in expired young adult carriers of the APOE epsilon4 allele, the major late-onset Alzheimer's susceptibility gene J Alzheimers Dis 2010 22 307 313 20847408 PMC3124564 source
plainstates an association- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Another study catalogued low abundance heteroplasmic mutations in COX1, a COX subunit gene located on the mtDNA [110]. Multiple mutations were detected and the mutation frequency increased with age. For the most part each individual mutation was present in very low amounts, but the number of mutations seemed to have a cumulative impact as the quantity of COX1 mutations within a given brain correl”
§ Brain aging, Alzheimer's disease, and mitochondria > 5) Mitochondria and the Aging Brain
What the sources say
- Not checked yetcites [110] Lin MT Simon DK Ahn CH Kim LM Beal MF High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain Hum Mol Genet 2002 11 133 145 11809722
hedgedstates an association- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Many of these AD cybrid alterations recapitulate phenomena observed in AD brains and include increased oxidative stress, apoptosis markers, and processing of APP to Aβ [123].”
§ Brain aging, Alzheimer's disease, and mitochondria > 6) Mitochondria and Alzheimer’s Disease
What the sources say
- Not checked yetcites [123] Swerdlow RH Mitochondria and cell bioenergetics: Increasingly recognized components and a possible etiologic cause of Alzheimer’s disease Antioxid Redox Signal 2011 in press PMC3329949 21902597
plainstates an association- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Oxidative stress may partly account for mtDNA’s relatively high mutation rate; mtDNA acquires mutations at approximately 10 times the rate of nuclear DNA [121].”
§ Brain aging, Alzheimer's disease, and mitochondria > 5) Mitochondria and the Aging Brain
What the sources say
- Not checked yetcites [121] Mecocci P MacGarvey U Kaufman AE Koontz D Shoffner JM Wallace DC Beal MF Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain Ann Neurol 1993 34 609 616 8215249
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Within the brain, age-related mitochondrial changes include a decline in complex I (NADH:ubiquinone oxidoreductase) and complex IV (cytochrome oxidase; COX) activity, with preserved complex II (succinate dehydrogenase) activity [107].”
§ Brain aging, Alzheimer's disease, and mitochondria > 5) Mitochondria and the Aging Brain
What the sources say
- Not checked yetcites [107] Navarro A Boveris A The mitochondrial energy transduction system and the aging process Am J Physiol Cell Physiol 2007 292 C670 C686 17020935 source
plainstates an association- 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.
In the paper
“Spectrophotometric analysis of the holoenzyme reveals the absence of its high affinity cytochrome c binding site and an altered Km [129].”
§ Brain aging, Alzheimer's disease, and mitochondria > 6) Mitochondria and Alzheimer’s Disease
What the sources say
- Not checked yetcites [129] Parker WD Jr Parks JK Cytochrome c oxidase in Alzheimer’s disease brain: purification and characterization Neurology 1995 45 482 486 7898701
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This was directly demonstrated in cell culture experiments in which COX inhibition and ATP depletion both reduced non-amyloidogenic, α secretase-mediated APP processing [95, 96, 98].”
§ Brain aging, Alzheimer's disease, and mitochondria > 6) Mitochondria and Alzheimer’s Disease
What the sources say
- Not checked yetcites [95] Gabuzda D Busciglio J Chen LB Matsudaira P Yankner BA Inhibition of energy metabolism alters the processing of amyloid precursor protein and induces a potentially amyloidogenic derivative J Biol Chem 1994 269 13623 13628 8175797 source
- Not checked yetcites [96] Gasparini L Racchi M Benussi L Curti D Binetti G Bianchetti A Trabucchi M Govoni S Effect of energy shortage and oxidative stress on amyloid precursor protein metabolism in COS cells Neurosci Lett 1997 231 113 117 9291153 source
- Not checked yetcites [98] Webster MT Pearce BR Bowen DM Francis PT The effects of perturbed energy metabolism on the processing of amyloid precursor protein in PC12 cells J Neural Transm 1998 105 839 853 9869322 source
boostedstates a cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Mutations that potentially increase Aβ, or at least its 42 amino acid species (Aβ42), are found in very rare autosomal dominant AD kindreds that mostly develop AD before the age of 60 [145].”
§ Brain aging, Alzheimer's disease, and mitochondria > 7) Reconciling Brain Aging and Alzheimer’s Disease: The Mitochondrial Cascade Hypothesis
What the sources say
- Not checked yetcites [145] Swerdlow RH Pathogenesis of Alzheimer's disease Clin Interv Aging 2007 2 347 359 18044185 PMC2685260
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“In one study, COX protein was increased in tangle-free neurons, and reduced in tangle-containing neurons [140].”
§ Brain aging, Alzheimer's disease, and mitochondria > 6) Mitochondria and Alzheimer’s Disease
What the sources say
- Not checked yetcites [140] Nagy Z Esiri MM LeGris M Matthews PM Mitochondrial enzyme expression in the hippocampus in relation to Alzheimer-type pathology Acta Neuropathol 1999 97 346 354 10208273
plainstates an association- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Large numbers of elderly individuals develop a dementia syndrome and have enough plaques and tangles to qualify for an AD diagnosis [3].”
§ Brain aging, Alzheimer's disease, and mitochondria > 1. Introduction
What the sources say
- Not checked yetcites [3] Swerdlow RH Is aging part of Alzheimer's disease, or is Alzheimer's disease part of aging? Neurobiol Aging 2007 28 1465 1480 16876913
plainstates an association- 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
“A more conservative conclusion is that reduced CA1 neuron counts associate with dementia, and as long as an aging individual is not demented CA1 neuron counts should remain relatively constant.”
§ Brain aging, Alzheimer's disease, and mitochondria > 3. Alzheimer’s Disease Versus Brain Aging: Pathology Perspective
hedgedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“One in every eight persons over 65 is estimated to have AD, 40–50% past the age of 85 may have it, and in some very elderly subgroups the figure appears to surpass 50% [2, 6–8].”
§ Brain aging, Alzheimer's disease, and mitochondria > 1. Introduction
What the sources say
- Not checked yetcites [2] Alzheimer's Association 2011 Alzheimer’s disease facts and figures Alzheimer's and Dementia 2011 7 208 244 21414557
- Not checked yetcites [6] Evans DA Funkenstein HH Albert MS Scherr PA Cook NR Chown MJ Hebert LE Hennekens CH Taylor JO Prevalence of Alzheimer's disease in a community population of older persons Higher than previously reported, JAMA 1989 262 2551 2556 2810583
- Not checked yetcites [7] Yaffe K Middleton LE Lui LY Spira AP Stone K Racine C Ensrud KE Kramer JH Mild cognitive impairment, dementia, and their subtypes in oldest old women Arch Neurol 2011 68 631 636 21555638 PMC3108074
- Not checked yetcites [8] Corrada MM Brookmeyer R Berlau D Paganini-Hill A Kawas CH Prevalence of dementia after age 90: results from the 90+ study Neurology 2008 71 337 343 18596243
hedged- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“According to some studies its incidence and prevalence continuously increases with advancing age, and appears to reach a point at which a majority of those beyond a certain age likely have it [3, 8, 12].”
§ Brain aging, Alzheimer's disease, and mitochondria > 1. Introduction
What the sources say
- Not checked yetcites [3] Swerdlow RH Is aging part of Alzheimer's disease, or is Alzheimer's disease part of aging? Neurobiol Aging 2007 28 1465 1480 16876913
- Not checked yetcites [8] Corrada MM Brookmeyer R Berlau D Paganini-Hill A Kawas CH Prevalence of dementia after age 90: results from the 90+ study Neurology 2008 71 337 343 18596243
- Not checked yetcites [12] Corrada MM Brookmeyer R Paganini-Hill A Berlau D Kawas CH Dementia incidence continues to increase with age in the oldest old: the 90+ study Ann Neurol 2010 67 114 121 20186856 PMC3385995 source
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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
“The biggest difference between these two syndromes is that AACD implies changes are due to brain aging and of minimal concern, while MCI implies changes are not due to brain aging and are of substantial concern (Figure 1).”
§ Brain aging, Alzheimer's disease, and mitochondria > 2. Alzheimer’s Disease Versus Brain Aging: Clinical Perspective
plainstates a cause- 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.
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
“Basing mechanistic inferences on descriptive observation is notoriously unreliable; such inferences are frequently inaccurate and occasionally misleading.”
§ Brain aging, Alzheimer's disease, and mitochondria > 4) Brain Aging and the New Alzheimer’s Disease Diagnostic Criteria
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no 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
“Also, since most young individuals will develop Aβ deposits if they live long enough [9, 54, 79], almost the entire population that doesn’t already have AD is on their way to developing AD [3].”
§ Brain aging, Alzheimer's disease, and mitochondria > 4) Brain Aging and the New Alzheimer’s Disease Diagnostic Criteria
What the sources say
- Not checked yetcites [9] Polvikoski T Sulkava R Rastas S Sutela A Niinisto L Notkola IL Verkkoniemi A Viramo P Juva K Haltia M Incidence of dementia in very elderly individuals: a clinical, neuropathological and molecular genetic study Neuroepidemiology 2006 26 76 82 16352910 source
- Not checked yetcites [54] Arriagada PV Marzloff K Hyman BT Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer's disease Neurology 1992 42 1681 1688 1307688 source
- Not checked yetcites [79] Delaere P He Y Fayet G Duyckaerts C Hauw JJ Beta A4 deposits are constant in the brain of the oldest old: an immunocytochemical study of 20 French centenarians Neurobiol Aging 1993 14 191 194 8487921 source
- Not checked yetcites [3] Swerdlow RH Is aging part of Alzheimer's disease, or is Alzheimer's disease part of aging? Neurobiol Aging 2007 28 1465 1480 16876913
plainstates a cause- 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
“According to the new criteria, the primary dividing line between AD and brain aging is the presence or absence of brain or CSF Aβ changes.”
§ Brain aging, Alzheimer's disease, and mitochondria > 4) Brain Aging and the New Alzheimer’s Disease Diagnostic Criteria
What the sources say
- Not checked yetcites [77] Sperling RA Aisen PS Beckett LA Bennett DA Craft S Fagan AM Iwatsubo T Jack CR Jr Kaye J Montine TJ Park DC Reiman EM Rowe CC Siemers E Stern Y Yaffe K Carrillo MC Thies B Morrison-Bogorad M Wagster MV Phelps CH Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease Alzheimers Dement 2011 7 280 292 21514248 PMC3220946 source
plainstates an association- 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.
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
“Findings such as these suggest reduced AD COX activity develops either very early in the course of AD, or that low COX activity represents an inherited AD risk factor.”
§ Brain aging, Alzheimer's disease, and mitochondria > 6) Mitochondria and Alzheimer’s Disease
hedgedstates a possible cause- 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 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 form of AD is mutation-dependent, not age-related.”
§ Brain aging, Alzheimer's disease, and mitochondria > 7) Reconciling Brain Aging and Alzheimer’s Disease: The Mitochondrial Cascade Hypothesis
plainstates a cause- 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
“Eventually, a point is reached where adaptive changes are no longer adequate or attempted. At this point neurodegeneration and clinical dementia result, and brain aging segues into AD.”
§ Brain aging, Alzheimer's disease, and mitochondria > 7) Reconciling Brain Aging and Alzheimer’s Disease: The Mitochondrial Cascade Hypothesis
What the sources say
- Not checked yetcites [123] Swerdlow RH Mitochondria and cell bioenergetics: Increasingly recognized components and a possible etiologic cause of Alzheimer’s disease Antioxid Redox Signal 2011 in press PMC3329949 21902597
- Not checked yetcites [146] Swerdlow RH Burns JM Khan SM The Alzheimer's disease mitochondrial cascade hypothesis J Alzheimers Dis 2010 20 Suppl 2 S265 S279 20442494 PMC2883665
- Not checked yetcites [147] Swerdlow RH Khan SM A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease Med Hypotheses 2004 63 8 20 15193340
- Not checked yetcites [148] Swerdlow RH Khan SM The Alzheimer's disease mitochondrial cascade hypothesis: an update Exp Neurol 2009 218 308 315 19416677 PMC2710413
plainstates a cause- 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 authors state this as an assumption: Brain aging and Alzheimer’s disease are mechanistically related.
None of the sources cited for this claim have been checked yet.
In the paper
“Also, even if anti-Aβ treatments are ultimately found to meaningfully benefit early-onset, autosomal dominant AD patients, this approach may turn out not to benefit or only minimally benefit late-onset, non-autosomal dominant AD patients.”
§ Brain aging, Alzheimer's disease, and mitochondria > 7) Reconciling Brain Aging and Alzheimer’s Disease: The Mitochondrial Cascade Hypothesis
What the sources say
- Not checked yetcites [123] Swerdlow RH Mitochondria and cell bioenergetics: Increasingly recognized components and a possible etiologic cause of Alzheimer’s disease Antioxid Redox Signal 2011 in press PMC3329949 21902597
- Not checked yetcites [146] Swerdlow RH Burns JM Khan SM The Alzheimer's disease mitochondrial cascade hypothesis J Alzheimers Dis 2010 20 Suppl 2 S265 S279 20442494 PMC2883665
- Not checked yetcites [147] Swerdlow RH Khan SM A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease Med Hypotheses 2004 63 8 20 15193340
- Not checked yetcites [148] Swerdlow RH Khan SM The Alzheimer's disease mitochondrial cascade hypothesis: an update Exp Neurol 2009 218 308 315 19416677 PMC2710413
hedgedstates a possible cause- 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 authors state this as an assumption: Brain aging and Alzheimer’s disease are mechanistically related.
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 changes alter bioenergetic metabolism and would predictably increase Aβ production.”
§ Brain aging, Alzheimer's disease, and mitochondria > 7) Reconciling Brain Aging and Alzheimer’s Disease: The Mitochondrial Cascade Hypothesis
hedgedstates a cause- 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: unclear — It is unclear why the paper says 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
“A case can be made that similar to what is observed in non-demented aged subjects, the brains of AD subjects show perturbed mitochondrial function and a subsequent compensatory response. Perhaps the main differences are that in AD brains defects are more profound, compensation is often inadequate, and compensatory responses are more likely to simply break down.”
§ Brain aging, Alzheimer's disease, and mitochondria > 6) Mitochondria and Alzheimer’s Disease
hedgedstates a possible cause- 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 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
“If as stipulated Aβ levels are the primary cause of late-onset AD then other, more upstream events cannot determine Aβ levels.”
§ Brain aging, Alzheimer's disease, and mitochondria > 7) Reconciling Brain Aging and Alzheimer’s Disease: The Mitochondrial Cascade Hypothesis
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
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
“APP processing, though, is a highly regulated event.”
§ Brain aging, Alzheimer's disease, and mitochondria > 7) Reconciling Brain Aging and Alzheimer’s Disease: The Mitochondrial Cascade Hypothesis
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: 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.
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 data imply APP processing is a highly regulated process, and suggests cell bioenergetics at least partly regulate APP processing.”
§ Brain aging, Alzheimer's disease, and mitochondria > 6) Mitochondria and Alzheimer’s Disease
hedgedstates a possible cause- 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 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
“- New definitions of Alzheimer’s disease infer most very elderly individuals have some form of it.”
§ Brain aging, Alzheimer's disease, and mitochondria > 8) Conclusions
plainstates an association- 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.
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
“- Whether Alzheimer’s disease and brain aging are mechanistically linked is contentious.”
§ Brain aging, Alzheimer's disease, and mitochondria > 8) Conclusions
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The other paradigm alternatively postulates in late-onset, non-autosomal dominant AD Aβ accumulates because of a more upstream physiologic process, Aβ accumulation marks this upstream process, and reducing Aβ will only benefit patients if Aβ itself also induces neurodysfunction.”
§ Brain aging, Alzheimer's disease, and mitochondria > 8) Conclusions
What the sources say
- Not checked yetcites [123] Swerdlow RH Mitochondria and cell bioenergetics: Increasingly recognized components and a possible etiologic cause of Alzheimer’s disease Antioxid Redox Signal 2011 in press PMC3329949 21902597
- Not checked yetcites [146] Swerdlow RH Burns JM Khan SM The Alzheimer's disease mitochondrial cascade hypothesis J Alzheimers Dis 2010 20 Suppl 2 S265 S279 20442494 PMC2883665
- Not checked yetcites [147] Swerdlow RH Khan SM A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease Med Hypotheses 2004 63 8 20 15193340
- Not checked yetcites [148] Swerdlow RH Khan SM The Alzheimer's disease mitochondrial cascade hypothesis: an update Exp Neurol 2009 218 308 315 19416677 PMC2710413
plainstates an association- Asserted: fails — The authors may not 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. The authors may not put it forward as true.
None of the sources cited for this claim have been checked yet.
In the paper
“An alternative to the amyloid cascade hypothesis [141–143], the mitochondrial cascade hypothesis [123, 146–148], sees brain aging and AD as part of a continuum.”
§ Brain aging, Alzheimer's disease, and mitochondria > 8) Conclusions
What the sources say
- Not checked yetcites [123] Swerdlow RH Mitochondria and cell bioenergetics: Increasingly recognized components and a possible etiologic cause of Alzheimer’s disease Antioxid Redox Signal 2011 in press PMC3329949 21902597
- Not checked yetcites [146] Swerdlow RH Burns JM Khan SM The Alzheimer's disease mitochondrial cascade hypothesis J Alzheimers Dis 2010 20 Suppl 2 S265 S279 20442494 PMC2883665
- Not checked yetcites [147] Swerdlow RH Khan SM A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease Med Hypotheses 2004 63 8 20 15193340
- Not checked yetcites [148] Swerdlow RH Khan SM The Alzheimer's disease mitochondrial cascade hypothesis: an update Exp Neurol 2009 218 308 315 19416677 PMC2710413
plainstates an association- 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.
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 other paradigm alternatively postulates in late-onset, non-autosomal dominant AD Aβ accumulates because of a more upstream physiologic process, Aβ accumulation marks this upstream process, and reducing Aβ will only benefit patients if Aβ itself also induces neurodysfunction.”
§ Brain aging, Alzheimer's disease, and mitochondria > 8) Conclusions
plainstates a possible cause- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The other paradigm alternatively postulates in late-onset, non-autosomal dominant AD Aβ accumulates because of a more upstream physiologic process, Aβ accumulation marks this upstream process, and reducing Aβ will only benefit patients if Aβ itself also induces neurodysfunction.”
§ Brain aging, Alzheimer's disease, and mitochondria > 8) Conclusions
What the sources say
- Not checked yetcites [123] Swerdlow RH Mitochondria and cell bioenergetics: Increasingly recognized components and a possible etiologic cause of Alzheimer’s disease Antioxid Redox Signal 2011 in press PMC3329949 21902597
- Not checked yetcites [146] Swerdlow RH Burns JM Khan SM The Alzheimer's disease mitochondrial cascade hypothesis J Alzheimers Dis 2010 20 Suppl 2 S265 S279 20442494 PMC2883665
- Not checked yetcites [147] Swerdlow RH Khan SM A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease Med Hypotheses 2004 63 8 20 15193340
- Not checked yetcites [148] Swerdlow RH Khan SM The Alzheimer's disease mitochondrial cascade hypothesis: an update Exp Neurol 2009 218 308 315 19416677 PMC2710413
plainstates a cause- Asserted: fails — The authors may not 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. The authors may not put it forward as true.
The authors state this as an assumption.
Brain aging and Alzheimer’s disease are mechanistically related.
“Rather than assuming brain aging and AD are mechanistically divergent phenomena, the mitochondrial cascade hypothesis assumes brain aging and AD are mechanistically related.”
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?
In the citing paper
“one literature- based analysis concludes 85% of those over 85 meet at least one of the new AD criteria [26].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [26]
Citations
Cites
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“represents the dementia syndrome's central characteristic, additional criteria are specified and must be satisfied [13,14].”
BackgroundMcKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.005 · Cited by 18,657 · cited 1×
“While cognitive decline represents the dementia syndrome’s central characteristic, additional criteria are specified and must be satisfied [13, 14].”
BackgroundThe Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., Gamst, A., Holtzman, D. M., Jagust, W. J., Petersen, R. C., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.008 · Cited by 10,152 · cited 1×
“Those who meet MCI clinical criteria and have Aβ changes qualify for a diagnosis of “MCI due to AD” [35] or “prodromal AD” [87].”
Mild Cognitive Impairment: Clinical Characterization and Outcome
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1999) · Archives of Neurology · doi:10.1001/archneur.56.3.303 · Cited by 8,980
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484 · cited 1×
“It was formulated in the early 1990s after an APP mutation was discovered in an autosomal dominant AD kindred [141,142].”
BackgroundSperling, R. A., Aisen, P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., Iwatsubo, T., Jack, C. R., Kaye, J., Montine, T. J., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.003 · Cited by 7,155 · cited 6×
“This is accomplished by stipulating everyone with either fibrillar Aβ deposits or low CSF Aβ has AD, or at least a modified form of AD [77].”
BackgroundResultInfluentialWinblad, B., Palmer, K., Kivipelto, M., Jelic, V., Fratiglioni, L., Wahlund, L. ‐., Nordberg, A., Bäckman, L., Albert, M., Almkvist, O., et al. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01380.x · Cited by 4,946 · cited 1×
“no dementia) [32–35].”
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70299-6 · Cited by 4,806 · cited 1×
“This is based on studies that suggest fi brillar A β deposition or low CSF A β either can or does precede the other changes [76,89].”
BackgroundCurrent concepts in mild cognitive impairment
Petersen, R. C., Doody, R., Kurz, A., Mohs, R. C., Morris, J. C., Rabins, P. V., Ritchie, K., Rossor, M., Thal, L., & Winblad, B. (2001) · Archives of Neurology · doi:10.1001/archneur.58.12.1985 · Cited by 4,781 · cited 1×
“no dementia) [32–35].”
Research works printed but not linked: 2
- White, 2011, Dissonance in diagnoses of dementia type during life with attribution determined at autopsy in the Honolulu-Asia Aging Study; impact of high prevalence of mixed pathology and specificity/non-specificity of clinical manifestations in the very old, Neurology, PL01.002
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Cited by
Sorted by citations
Items 201–300 of 305
Sharma, Y., & Garabadu, D. (2020) · Experimental Brain Research · doi:10.1007/s00221-020-05896-7 · Cited by 15
“2010; Swerdlow 2011).”
BackgroundRetractedDhull, D. K., & Kumar, A. (2017) · Inflammopharmacology · doi:10.1007/s10787-017-0431-3 · Cited by 15
“Mitochondrial impairment is also known to be an early feature of aging and AD (Wang et al. 2009; Swerdlow 2011).”
BackgroundIvancic, V. A., Krasinski, C. A., Zheng, Q., Meservier, R. J., Spratt, D. E., & Lazo, N. D. (2018) · Bioscience Reports · doi:10.1042/bsr20181416 · Cited by 15
“Because l eve l s of ATP d ec l ine with ageing or mitochon d ria l impairment [ 44 , 45] , our resu l ts as summarize d in Tab l e 1 , suggest that preventative strategies aime d at maintaining the norma l l eve l s of ATP an d M g 2 + may boost the ID E -d epen d ent c l earance of A β 4 2…”
Altering Mitochondrial Dysfunction as an Approach to Treating Alzheimer’s Disease
Colca, J. R., & Feinstein, D. L. (2012) · Advances in pharmacology · doi:10.1016/b978-0-12-394816-8.00005-2 · Cited by 14
“More comprehensive reviews of this topic can be found in several recent reviews (Tillement et al., 2011; Muller et al., 2010; Swerdlow et al., 2010; Swerdlow 2011; Reddy 2011).”
BackgroundThe Role of Aging in Alzheimer’s Disease
Kerchner, G. A., & Wyss‐Coray, T. (2015) · Springer eBooks · doi:10.1007/978-3-319-23246-1_7 · Cited by 14
A unique combination of micronutrients rejuvenates cognitive performance in aged mice
Perez, S. D., Du, K., Rendeiro, C., Wang, L., Wu, Q., Rubakhin, S. S., Vazhappilly, R., Baxter, J. H., Sweedler, J. V., & Rhodes, J. S. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.11.019 · Cited by 14
“…University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, USA Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, USA Department of Chemistry, University of…”
BackgroundA comparison of the mitochondrial proteome and lipidome in the mouse and long-lived Pipistrelle bats
Pollard, A. K., Ingram, T. L., Ortori, C. A., Shephard, F., Brown, M., Liddell, S., Barrett, D. A., & Chakrabarti, L. (2019) · Aging · doi:10.18632/aging.101861 · Cited by 14
Wang, H., Li, L., Jia, K., Wang, Q., Sui, S., Lin, Y., & He, Y. (2020) · Neuroreport · doi:10.1097/wnr.0000000000001526 · Cited by 14
Gauba, E., Sui, S., Tian, J., Driskill, C. M., Jia, K., Yu, C., Rughwani, T., Wang, Q., Kroener, S., Guo, L., et al. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.09.018 · Cited by 15
Ávila, J., de Barreda, E. G., Pallas‐Bazarra, N., & Hernández, F. (2013) · Europe PMC (PubMed Central) · doi:10.13039/501100006373 · Cited by 15
Gao, C., Shang, J., Sun, Z., Xia, M., Gao, D., Sun, R., Li, W., Wang, F., & Zhang, J. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03858-y · Cited by 13
Towards a Unitary Hypothesis of Alzheimer’s Disease Pathogenesis
Área-Gómez, E., & Schon, E. A. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-231318 · Cited by 18
“Finally, mitochondrial bioenergetics [35] and organelle morphology and dynamics—most notably the balance between organellar fusion and fission—which are also altered in AD [213, 214], are MAM-mediated functions.”
BackgroundNeuroprotective compounds of Tilia amurensis
Ma, C. J., Lee, B., Weon, J., Eom, M., & Jung, Y. (2015) · Pharmacognosy Magazine · doi:10.4103/0973-1296.166065 · Cited by 13
“AD is a most common form of dementia in people over the age of 65.[1] Pathogenesis of AD is characterized by extracellular deposits of amyloid‐beta and the intracellular neurofibrillary tangles in the brain.”
BackgroundEvolving Evidence of Calreticulin as a Pharmacological Target in Neurological Disorders
Kotian, V., Sarmah, D., Kaur, H., Kesharwani, R., Verma, G., Mounica, L., Veeresh, P., Kalia, K., Borah, A., Wang, X., et al. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00158 · Cited by 12
Fan, Y., Zeng, F., Brown, R. W., Price, J. B., Jones, T. C., & Zhu, M. (2020) · Neurotoxicity Research · doi:10.1007/s12640-020-00250-9 · Cited by 13
“As aging is considered a major risk for the degenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD) (Rodriguez et al. 2015; Swerdlow 2011), to elucidate effects of these transcription factors in aged animals may also provide interesting information for the treatment…”
BackgroundCurley, D. E., Webb, A. E., Sheffler, D. J., & Haass‐Koffler, C. L. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.786855 · Cited by 14
“Corticotropin releasing factor binding protein has been suggested as a molecular mechanism linking stress and agerelated neurodegenerative disorders, particularly Alzheimer’s disease (AD) (Vandael and Gounko, 2019).”
BackgroundInfluentialCampos, J. M. B., da Costa, M. D. A., de Rezende, V. L., Costa, R. R. N., Ebs, M. F. P., Behenck, J. P., Casagrande, L. D. R., Venturini, L. M., Silveira, P. C. L., Réus, G. Z., et al. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04491-z · Cited by 13
“Oxidative stress is caused by the imbalance of reactive oxygen/nitrogen species (ROS/RNS) production and the body’s ability to buffer these deleterious effects through antioxidative systems [19].”
Peripheral vascular dysfunction and the aging brain
Wahl, D., & Clayton, Z. S. (2024) · Aging · doi:10.18632/aging.205877 · Cited by 12
“Mitochondrial dysfunction, characterized in part by excessive mitochondrial ROS production, is also highly implicated in brain aging [72, 73], which has been reviewed in detail elsewhere [74].”
BackgroundNeshan, M., Campbell, A., Malakouti, S. K., Zareei, M., & Ahangari, G. (2020) · Heliyon · doi:10.1016/j.heliyon.2020.e04716 · Cited by 13
Nicolson, G. L., Settineri, R. A., & Ellithorpe, R. R. (2014) · Functional Foods in Health and Disease · doi:10.31989/ffhd.v4i1.26 · Cited by 13
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Osborne, O., Kowalczyk, J., Louis, K. D. P., Daftari, M., Colbert, B., Naranjo, O., Torices, S., Andras, I. E., Dykxhoorn, D. M., & Toborek, M. J. (2022) · Extracellular Vesicles and Circulating Nucleic Acids · doi:10.20517/evcna.2022.22 · Cited by 11
“Alzheimer’s disease (AD) is the most common neurodegenerative disease, affecting one in every eight people over the age of 65 and around half of the individuals over the age of 85[1].”
Genetic Analysis of Mitochondrial Ribosomal Proteins and Cognitive Aging in Postmenopausal Women
Mozhui, K., Snively, B. M., Rapp, S. R., Wallace, R. B., Williams, R. W., & Johnson, K. (2017) · Frontiers in Genetics · doi:10.3389/fgene.2017.00127 · Cited by 11
“Mitochondrial function has been central to aging research and dysfunctions in this organelle have been implicated in lifespan regulation, cognitive aging, and Alzheimer’s disease (Bishop et al., 2010; Swerdlow, 2011; Picard and McEwen, 2014).”
BackgroundWang, J., He, M., Guo, W., Zhang, Y., Sui, X., Lin, J., Liu, X., Li, H., Li, J., Yang, Q., et al. (2021) · BioMed Research International · doi:10.1155/2021/6649085 · Cited by 10
RetractedDo Sleep Disturbances have a Dual Effect on Alzheimer’s Disease?
Arjmandi-Rad, S., Ebrahimnejad, M., Zarrindast, M., & Vaseghi, S. (2022) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-022-01228-1 · Cited by 11
“In aging and AD, progressive dysfunction of mitochondrial function has been declared as the primary cause of ROS production and accumulation (Swerdlow 2011).”
BackgroundTortuous Paths of Insulin Signaling and Mitochondria in Alzheimer’s Disease
Carvalho, C., Cardoso, S., Correia, S. C., & Moreira, P. I. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-3540-2_9 · Cited by 10
Molecular and Biochemical Pathways Encompassing Diabetes Mellitus and Dementia
Behl, T., Arora, A., Sehgal, A., Singh, S., Sharma, N., Bhatia, S., Al‐Harrasi, A., BUNGAU, S. G., & Mostafavi, E. (2021) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527320666211110115257 · Cited by 9
In vitro salicylate does not further impair aging-induced brain mitochondrial dysfunction
Marques‐Aleixo, I., Rocha‐Rodrigues, S., Alves, E. S., Coxito, P. M., Passos, E., Oliveira, P. J., Magalhães, J., & Ascensão, A. A. M. R. (2012) · Toxicology · doi:10.1016/j.tox.2012.07.018 · Cited by 10
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“Assuming that aging and AD are part of a continuum 36,39 , some mechanistic links could underlie these two conditions which in turn raises the possibility that aging could adopt an aggravated trajectory toward mild cognitive impairment (MCI) or even dementia by converting into AD when under the…”
Losartan Mitigates Oxidative Stress in the Brains of Aged and Inflamed IL-10−/− Mice
Saleh, N., Coşarderelioğlu, Ç., Vajapey, R. S., Walston, J. D., & Abadir, P. M. (2022) · The Journals of Gerontology Series A · doi:10.1093/gerona/glac101 · Cited by 8
In Utero Exposure to Air Pollutants and Mitochondrial Heteroplasmy in Neonates.
Cosemans, C., Wang, C.-R., Martens, D., Janssen, B., Vanpoucke, C., Lefebvre, W., Smeets, K., Nawrot, T., & Plusquin, M. (2022) · Environmental Science and Technology · doi:10.1021/acs.est.2c02556 · Cited by 9
β‐Apptists and Tauists, it is time for a sermon from the book of biogenesis
Swerdlow, R. H. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07561.x · Cited by 8
“Mitochondria are increasingly believed to play a role in Alzheimer’s disease (AD) (Swerdlow 2011b).”
BackgroundSelf-citationThe meaning of sexuality for the spouse caregiver of the elderly person with Alzheimer’s disease
Sales, M. G. S., & Menezes, T. M. D. O. (2017) · Rev Rene · doi:10.15253/2175-6783.2017000200009 · Cited by 8
Niu, J., Liu, Y., Wang, W., & Lin, W. (2019) · Journal of Photochemistry and Photobiology A Chemistry · doi:10.1016/j.jphotochem.2019.04.008 · Cited by 8
Efavirenz is associated with altered fronto-striatal function in HIV+ adolescents
du Plessis, S., Perez, A., Fouché, J., Phillips, N. J., Joska, J. A., Vink, M., Myer, L., Zar, H. J., Stein, D. J., & Hoare, J. (2019) · Journal of NeuroVirology · doi:10.1007/s13365-019-00764-9 · Cited by 8
“It is known that mitochondria disfunction impacts cell survival and has been associated with ageing and dementing processes (Swerdlow 2011).”
Kim, B.-H., Lee, H., Ham, H., Kim, H. J., Jang, H., Kim, J. P., Park, Y. H., Kim, M., & Seo, S. W. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1278998 · Cited by 6
“Furthermore, the SCRN2, MRPL10 , and OSBPL7 are related to proteolysis, mitochondrial translation, and cholesterol metabolism, respectively, which play important roles in AD pathogenesis (Bishop et al., 2010; Strooper, 2010; Swerdlow, 2011; Picard and McEwen, 2014; Xue et al., 2018).”
BackgroundAn Integrative Overview of Non-Amyloid and Non-Tau Pathologies in Alzheimer’s Disease
Menta, B. W., & Swerdlow, R. H. (2018) · Neurochemical Research · doi:10.1007/s11064-018-2603-y · Cited by 7
Self-citationla Cruz, D. D. G.-D., Juárez‐Rojop, I. E., Tovilla‐Zárate, C. A., Nicolini, H., & Mendoza, A. D. G. (2024) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s460554 · Cited by 6
“6,7 Mitochondrial dysfunction has been associated with neurodegenerative (Alzheimer's disease, Parkinson's disease) and neuropsychiatric disorders like depression, anxiety, and schizophrenia.”
BackgroundInflammatory injury and mitophagy of the brain in chicken exposed to Cr(VI)
Guo, S., Wang, X., Wang, L., Cheng, G., Zhang, M., Xing, Y., Zhao, X., Liu, Y., & Liu, J. (2021) · Environmental Science and Pollution Research · doi:10.1007/s11356-021-13675-2 · Cited by 6
“…Na+ K+-ATPase, Mg2+-ATPase, and Ca2+-ATPase activities decreased significantly in the brain cells with increasing Cr(VI) doses, indicating that the mitochondria damaged by Cr(VI) influenced mitochondrial enzyme activities and the normal functions of cells in the chicken brains (Swerdlow 2011).”
BackgroundQian, J., Li, Y., Wang, Y., Ye, Q., & Luo, H.-B. (2023) · Redox Report · doi:10.1080/13510002.2023.2259246 · Cited by 6
“Studies have shown that excess H 2 O 2 activates stress-sensi-tive kinases (such as JNK and IKK), causing insulin resistance and resulting in inadequate energy supply in brain tissue [24].”
BackgroundBreastfeeding predicts blood mitochondrial DNA content in adolescents
Cosemans, C., Nawrot, T. S., Janssen, B. G., Vriens, A., Smeets, K., Baeyens, W., Bruckers, L. M., Hond, E. D., Loots, I., Nelen, V., et al. (2020) · Scientific Reports · doi:10.1038/s41598-019-57276-z · Cited by 6
Avetisyan, A. V., Balasanyants, S. M., Simonyan, R. A., Koroev, D. O., Kamynina, A. V., Zinovkin, R. A., Бобкова, Н. В., & Volpina, O. M. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104799 · Cited by 6
The Ageing Brain, Mitochondria and Neurodegeneration
Hudson, G. (2016) · Springer eBooks · doi:10.1007/978-3-319-28637-2_3 · Cited by 5
Heydari, M., Hojati, Z., & Dehbashi, M. (2021) · PubMed Central · doi:10.22074/cellj.2021.7047 · Cited by 5
“Investigations on postmortem AD brains showed that is mainly relied on intracellular neurofibrillary tangles (NFTs), extracellular (Amyloid β) Aβ plaques, synaptic damage, loss of synapses, loss of synaptic proteins, proliferation of reactive astrocytes and activated microglia, deficiency in cholinergic neurons, an ag…”
BackgroundSwinter, K., Salah, D., Rathnayake, R., & Gunawardena, S. (2023) · Cells · doi:10.3390/cells12192406 · Cited by 5
“The resulting supernatant was then denatured (NuPAGE LDS), run on 10% Bis-Tris gels (Invitrogen/Thermo Fisher, Waltham, MA) and used for Western blotting (DRP1, 1:250 [23], MFN, 1:100 [24], or Tubulin, 1:1000, Abcam, Cambridge, UK).”
BackgroundMethodComparative functional genomic analysis of Alzheimer’s affected and naturally aging brains
Peng, Y.-S., Tang, C.-W., Peng, Y.-Y., Chang, H., Chen, C., Guo, S., Wu, L.-C., Huang, M.-C., & Lee, H.-C. (2020) · PeerJ · doi:10.7717/peerj.8682 · Cited by 5
Targeting dysregulation of brain iron homeostasis in ageing
Weinreb, O., Amit, T., & Youdim, M. B. H. (2012) · Nutrition and Aging · doi:10.3233/nua-2012-0003 · Cited by 5
“[109] Swerdlow RH.”
Kang, C., Park, M., & Lee, H. (2023) · Molecular & Cellular Toxicology · doi:10.1007/s13273-023-00401-x · Cited by 4
The Different Molecular Targets and Its Significant Role in Alzheimer’s Disease: A Review
Perumal, D. P., & Pichaivel, M. (2024) · Asian Journal of Medicine and Biomedicine · doi:10.37231/ajmb.2024.8.1.650 · Cited by 4
The Effects of Virgin Coconut Oil on Prevention of Alzheimer’s Disease
Mirzaei, F., Khazaei, M., Komaki, A., Amiri, I., & Jalili, C. (2019) · Jundishapur Journal of Natural Pharmaceutical Products · doi:10.5812/jjnpp.67747 · Cited by 4
“Alzheimer’s disease (AD) and obesity are related factors that are recognized as the two main health problems (1, 2).”
BackgroundLane, J., & Fontaine, K. R. (2021) · OBM Integrative and Complementary Medicine · doi:10.21926/obm.icm.2102015 · Cited by 5
“, impaired glucose utilization in the brain) indicative of a “starving” brain [82].”
BackgroundTsybul’ko, E. A., Krementsova, A. V., Symonenko, A. V., Rybina, O. Y., Roshina, N. V., & PASYUKOVA, E. G. (2016) · The Journals of Gerontology Series A · doi:10.1093/gerona/glw084 · Cited by 6
Nguyen, T., Diaz, D., & Drăghici, S. (2016) · ACM International Conference on Bioinformatics, Computational Biology, and Health Informatics (ACM-BCB) · doi:10.1145/2975167.2975168 · Cited by 4
“The common elements include abnormal protein folding, endoplasmic reticulum stress, and ubiquitin mediated breakdown of proteins, leading to programmed cell death [43, 44, 45, 46].”
BackgroundWu, X., Li, X., Liang, S., Liu, Y., Dai, X., Zheng, Q., & Sun, Y. (2017) · Preprints.org · doi:10.20944/preprints201705.0144.v1 · Cited by 4
“As the main source of ROS and major target of oxidative damage, progressive impairment of mitochondrial function has been implicated in AD [14].”
BackgroundMtDNA‐depleted neuronal cell transcriptomes reveal Alzheimer's disease‐related changes
Menta, B. W., Schueddig, E., Ranjan, A., Li, Y., Andrews, S. J., Wilkins, H., Pei, D., & Swerdlow, R. H. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70929 · Cited by 4
“1,3 In experimental models, primary mitochondrial dysfunction alters amyloid precursor protein (APP), amyloid beta (A β ), microtubule-associated protein tau (MAPT), and apolipoprotein E (APOE) biology, 4–7 which suggests mitochondrial dysfunction could perhaps even initiate the disease, although…”
Self-citationBiomarkers of mitochondrial origin: a futuristic cancer diagnostic
Gayan, S., Joshi, G., & Dey, T. (2022) · Integrative Biology · doi:10.1093/intbio/zyac008 · Cited by 4
Unveiling FOXO3's metabolic contribution to menopause and Alzheimer's disease
O'Mahony, C., Hidalgo‐Lanussa, O., & Barreto, G. E. (2025) · Experimental Gerontology · doi:10.1016/j.exger.2025.112679 · Cited by 3
Enzymes and Alzheimer's Disease: Pioneering Drug Development Strategies
Godwa, T., Dubey, S., & Tiwari, P. K. (2025) · Current Psychopharmacologye · doi:10.2174/0122115560340307250106065419 · Cited by 3
Halma, M. T. J., Aniwar, M., Selem, E., Tuszyński, J. A., Varón, J., & Marik, P. E. (2025) · Archives of Gerontology and Geriatrics Plus · doi:10.1016/j.aggp.2025.100145 · Cited by 4
“…et al., 2012; Siasos et al., 2020), obesity (Li et al., 2017), and hypertension (Lahera et al., 2017), but also perhaps contribute to cardiovascular disease (Dai et al., 2012; North & Sinclair, 2012; Poznyak et al., 2020), cancer (Patel et al., 2020) and Alzheimer ’ s disease (Swerdlow, 2011).”
Peptides and Glycopeptides with Anti-Acetylcholinesterase Activity Obtained from Yeast Mannoproteins
Pablo, S. (2018) · International Journal of Microbiology and Biotechnology · doi:10.11648/j.ijmb.20180303.11 · Cited by 3
“Dementia is a clinical syndrome caused by disorders that affect the brain [5, 6], Alzheimer’s disease (AD) being the most common type of dementia [7, 8].”
BackgroundMitochondrial Dysfunction and Cancer
한유선, 제갈명은, & Kim, Y. J. (2019) · JoLS Journal of Life Sciences · doi:10.5352/jls.2019.29.9.1034 · Cited by 3
Liu, Q., Zhao, G., Zhou, C., et al. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.11.002 · Cited by 3
Brain-Resident Immune Cells in Neurodevelopmental Disorders
Pangrazzi, L., Weinberger, B., & Bozzi, Y. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-89525-8_10 · Cited by 2
Mendili, M., Smach, M. A., Husein, N., & Khadhri, A. (2020) · Avicenna Journal of Medical Biochemistry · doi:10.34172/ajmb.2020.10 · Cited by 2
“74 × 10−4 × A /CO (4) (R: rate in moles of substrate hydrolyzed/minute/mg protein; A: change in absorbance/min; and CO: original concentration of protein (mg/mL)).”
BackgroundAnti-Amnesic Effect of Curcumin Spray Dry Powders on Scopolamine-Induced Mouse Memory Impairment
Kim, D.-W., Choung, J. J., Shin, C. H., Chun, Y. S., Kim, J. K., Yun, N. K., Lee, H. J., Ku, S., & Seo, B. S. (2022) · Journal of the Korean Society of Food Science and Nutrition · doi:10.3746/jkfn.2022.51.8.751 · Cited by 2
Neuroprotective and Behavioral Benefits of Exogenous Ketone Supplementation-Evoked Ketosis
Kovács, Z., D’Agostino, D. P., & Ari, C. (2022) · Oxford University Press eBooks · doi:10.1093/med/9780197501207.003.0034 · Cited by 2
Organelle targeting: Focus on the mitochondria
Padh, H., Shenoy, S., Thakkar, S., & Misra, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-85666-9.00021-8 · Cited by 1
Mohamad, A. M., Hassan, S. A. M., Moussa, E. A., & Mahdy, T. O. E. (2024) · Anatomia Histologia Embryologia · doi:10.1111/ahe.13014 · Cited by 2
“…early stage of ageing resulting in the development of several age-dependent neurodegenerative disorders such as Parkinson's and Alzheimer's diseases (Bornstein & Daw, 2013; Freeman et al., 2017; Gray et al., 2018; Lin & Beal, 2006; Miller & O'Callaghan, 2005; O'Shea et al., 2016; Swerdlow, 2011).”
BackgroundAlgieri, C., Cugliari, A., Glogowski, P. A., Granata, S., Fabbri, M., Trombetti, F., Bacci, M. L., & Nesci, S. (2024) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2024.149528 · Cited by 1
Contribution of Nucleic Acids in the Pathogenesis of Alzheimer’s Disease
Farooqui, A. A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809937-7.00004-5 · Cited by 1
Exercise-Mediated Autophagy and Brain Aging
Kou, X., Zhang, H., Guo, Y. L., Kirberger, M., & Chen, N. (2021) · Springer eBooks · doi:10.1007/978-981-16-4525-9_6 · Cited by 1
Role of Glycogen Synthase Kinase 3 in Molecular Pathology of Alzheimer’s Disease
Gupta, A. (2022) · International Journal of Health Sciences and Pharmacy · doi:10.47992/ijhsp.2581.6411.0093 · Cited by 1
Effect of ketogenic diet on alzheimer's disease to improve cognitive function: A literature review
Khoiroh, A. D. (2023) · Malahayati International Journal of Nursing and Health Science · doi:10.33024/minh.v6i4.11557 · Cited by 1
“The ketogenic diet is high in fat and low in carbohydrates, promoting ketogenesis (Cunnane, Nugent, Roy, Courchesne-Loyer, Croteau, Tremblay, & Rapoport, 2011).”
BackgroundThe Role of Nitric Oxide on Vascular Dysfunction During Aging and Alzheimer’s Disease
Venturelli, M. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816545-4.00011-6 · Cited by 1
The ketogenic diet and healthy brain aging
Rogerson, G., & Preedy, V. R. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-817990-1.00049-4 · Cited by 1
Chauhan, B. S., Garai, S., Singh, J., & Srikrishna, S. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.16.492076 · Cited by 1
“Mitochondrial dysfunction was found in invertebrate engaged with a relatively short lifespan and progression of cognitive impairment during AD pathogenesis (Bishop et al., 2010; Swerdlow, 2011; Picard and McEwen, 2014).”
BackgroundDementia, Delirium, and Depression
Anderson, H. S. (2014) · Springer eBooks · doi:10.1007/978-1-4614-9047-0_6
“A competing hypothesis theorizes that the plaques and tangles are clinical outcomes, but the actual cause is mitochondrial dysfunction [ 10 , 11 ].”
BackgroundMild Cognitive Impairment: Beyond Memory Dysfunction
Tales, A., Bayer, A. J., Krajcik, S., & Jellinger, K. A. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/262305
Diagnostic Challenges in Mitochondrial Disease
Dabke, P., & Rao, P. (2012) · International Journal of Health and Rehabilitation Sciences (IJHRS) · doi:10.5455/ijhrs.00000005
Presenilin signalling in a basic biomedical model
Ludtmann, M. H. R. (2012)
Carvalho, C. (2013) · Estudo Geral (Universidade de Coimbra)
Biomarkers and progress of antioxidant therapy for rare mitochondrial disorders
Chico, L., Orsucci, D., Gerfo, A. L., Marconi, L., Mancuso, M., & Siciliano, G. (2016) · Expert Opinion on Orphan Drugs · doi:10.1080/21678707.2016.1178570
“ropathy (LHON); etc.[2] Several evidences indicate that mitochondrial dysfunction involves alteration of mitochondrial respiratory chain”
BackgroundIdentifying the mechanism of Aβ42 inhibition of PDGF-BB signalling
Saffi, G. T. (2014) · UWSpace (University of Waterloo)
Roy, N. (2015) · KU ScholarWorks (University of Kansas)
Deregulated MicroRNAs Associated With Alzheimer’s Disease
Temraz, D. (2018) · Southeast Europe Journal of Soft Computing · doi:10.21533/scjournal.v6i2.141
Dietas cetogénicas y su papel en la nutrición clínica
Lloreda, P. S. (2021) · Medicina · doi:10.56050/01205498.1607
Efeitos neuromodulatórios e neurotróficos da insulina sobre o envelhecimento cerebral
Haas, C. B. (2013) · Americanae (AECID Library)
Diet in Brain Health and Neurological Disorders: Risk Factors and Treatments
Brandt, J. (2019) · MDPI eBooks · doi:10.3390/books978-3-03921-651-2
Alzheimer’s disease as a syndrome of overloaded amyloidic synaptic tagging in memory networksPreprint
Murphy, N. (2021) · OSF Preprints (OSF Preprints) · doi:10.31219/osf.io/7gsaz
Lou, Y. (2022) · American Journal of Biomedical Science & Research · doi:10.34297/ajbsr.2022.15.002170
Chujan, S., Cholpraipimolrat, W., & Satayavivad, J. (2023) · Biochemical Genetics · doi:10.1007/s10528-023-10549-9
“Age-related cognitive impairments are symptoms of various brain disorders, most typically, Alzheimer’s disease (AD) (Swerdlow 2011).”
Defective Mitophagy and the Etiopathogenesis of Alzheimer’s Disease
Elbermawy, Y., & Abdelhameed, A. M. (2023) · Springer eBooks · doi:10.1007/978-981-19-3949-5_29-1
Structural diversity of mitochondria in the neuromuscular system across developmentPreprint
Bae, J. A., Choi, M.-K., Ahn, S., Ko, G., Choe, D. T., Yim, H., Nguyen, K. C. Q., Kim, J. S., Hall, D. H., & Lee, J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.19.604219
Defective Mitophagy and the Etiopathogenesis of Alzheimer’s Disease
Elbermawy, Y., & Abdelhameed, A. M. (2024) · Springer eBooks · doi:10.1007/978-981-99-7557-0_29
The biochemical pathways of Alzheimer's disease
El-Gammal, M. A., & Kodous, F. E. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15702-8.00001-4
Ahire, C. G., Yadav, R., Bhamare, U. U., Kaur, G., & Palkar, M. B. (2026) · The FASEB Journal · doi:10.1096/fj.202503317r · Cited by 2
Mitochondria, neurosteroids and biological rhythms : implications in health and disease states
Grimm, A. (2015) · theses.fr (ABES) · doi:10.70675/8aac5aa9z77cdz49bdz9cf5z0ff0b5dd0f84
Exploration de nouveaux biomarqueurs plasmatiques pour le diagnostic de la maladie d’Alzheimer
Rossi, E. (2021) · theses.fr (ABES) · doi:10.70675/71230be4z1955z4fafzb1b8z8ff71a4edaff
Metadata
- Authors
- Swerdlow, R. H.
- Affiliations
- University of Kansas (US)
- Corresponding author
- Swerdlow, Russell H.
- ORCID
- Swerdlow, Russell H.
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 1812
- Issue
- 12
- Pages
- 1630-1639
- ISSN
- 0925-4439 (ISSN-L)
- PMC
- PMC3210037
- OpenAlex
- W2107600848
- Semantic Scholar
- 27fa4335f66ebc5c5884c9fe5844e2bb4ba32ecb
- Cited by
- 306
- References
- 157
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 17 · 2023: 14 · 2022: 23 · 2021: 27 · 2020: 27 · 2019: 28 · 2018: 26 · 2017: 17 · 2016: 24 · 2015: 17 · 2014: 20 · 2013: 29 · 2012: 22
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- P30AG035982
- Morgan Family Foundation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- Alzheimer's disease, brain aging, mitochondria, amyloid-beta, bioenergetic stress, mitochondrial dysfunction, disease definition, molecular mechanisms, threshold hypothesis
- MeSH terms
- Aging, Alzheimer Disease, Brain, Humans, Mitochondria, Amyloid beta-Peptides
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