The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index; none of the 1 sources its claims cite is checked for support yet.
Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer’s Disease
Open accessAbstract
Background Individually, heart failure (HF) and Alzheimer's disease (AD) are severe threats to population health, and their potential coexistence is an alarming prospect. In addition to sharing analogous epidemiological and genetic profiles, biochemical characteristics, and common triggers, the authors recently recognized common molecular and pathological features between the 2 conditions. Whereas cognitive impairment has been linked to HF through perfusion defects, angiopathy, and inflammation, whether patients with AD present with myocardial dysfunction, and if the 2 conditions bear a common pathogenesis as neglected siblings are unknown. Objectives Here, the authors investigated whether amyloid beta (Aβ) protein aggregates are present in the hearts of patients with a primary diagnosis of AD, affecting myocardial function. Methods The authors examined myocardial function in a retrospective cross-sectional study from a cohort of AD patients and age-matched controls. Imaging and proteomics approaches were used to identify and quantify Aβ deposits in AD heart and brain specimens compared with controls. Cell shortening and calcium transients were measured on isolated adult cardiomyocytes. Results Echocardiographic measurements of myocardial function suggest that patients with AD present with an anticipated diastolic dysfunction. As in the brain, Aβ 40 and Aβ 42 are present in the heart, and their expression is increased in AD. Conclusions Here, the authors provide the first report of the presence of compromised myocardial function and intramyocardial deposits of Aβ in AD patients. The findings depict a novel biological framework in which AD may be viewed either as a systemic disease or as a metastatic disorder leading to heart, and possibly multiorgan failure. AD and HF are both debilitating and life-threatening conditions, affecting enormous patient populations. Our findings underline a previously dismissed problem of a magnitude that will require new diagnostic approaches and treatments for brain and heart disease, and their combination.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This study reports that patients with Alzheimer’s disease (AD) show anticipated diastolic myocardial dysfunction and that Aβ40/Aβ42 deposits are present in AD myocardium, where they are increased relative to controls. The authors propose that AD may involve the heart as part of a systemic or metastatic amyloid process.
Key findings
- AD was associated with earlier diastolic dysfunction: in the first age tertile, mitral valve E/A ratio was 1.20 ± 0.18 in AD vs. 1.34 ± 0.12 in controls, with a linear regression F-test p < 0.05; in the third tertile, values were 0.82 ± 0.08 vs. 0.86 ± 0.08.
- Left ventricular wall thickness and aortic valve peak velocity were increased only in older AD subjects: LVSWT 1.12 ± 0.05 vs. 1.01 ± 0.04 (p < 0.05), LVILT 1.07 ± 0.05 vs. 1.00 ± 0.03 (p < 0.05), and aortic valve peak velocity 2.44 ± 0.41 vs. 1.51 ± 0.14 (p < 0.05).
- Aβ40 and Aβ42 were present in heart and brain by immunoblotting and ELISA, with increased levels in AD patients compared with controls; heart levels were lower than brain levels.
- Immunogold TEM detected Aβ42-PAO/VIA-positive staining in AD myocardium, and isolated AD cardiomyocytes showed slower relaxation (R50 0.272 vs. 0.238) and prolonged Ca2+ transients (TTP 0.544 vs. 0.151; R90 0.328 vs. 0.084) compared with controls, though no statistical calculations were performed because only 3 cardiomyocytes from 1 AD case were measured.
Methods
- Retrospective cross-sectional clinical cohort of AD patients and age/sex/ethnicity-matched controls at a 1:2 ratio, excluding other underlying conditions affecting myocardial function; echocardiographic measures were analyzed with linear regression adjusted for age, exploratory age tertiles, Student t-tests, ordinary least squares, and ANOVA for beta-blocker therapy.
- A separate cohort provided fresh heart and brain specimens from 4 clinically diagnosed AD cases and controls; imaging included Thioflavin S, silver stain, A11 immunohistochemistry, transmission electron microscopy, and immunogold TEM with anti-Aβ42 and Aβ42-PAO VIA antibodies.
- Molecular quantification used immunoblotting and ELISA for Aβ peptides; adult left ventricular cardiomyocytes were isolated by enzymatic digestion, and contractility and Ca2+ transients were measured with video edge-detection and dual-excitation systems.
Limitations
- The paper states that sample numbers were limited for clinical, pathological, and molecular assessment; the cross-sectional design cannot infer temporality; cardiomyocyte function came from only 3 myocytes of the youngest AD case; brain samples were cortical only; detailed cardiac function was not always available; and E/E′ was unavailable retrospectively.
- Evident from the text: the AD tissue cohort was very small (4 cases), the cardiomyocyte comparison used 1 AD heart versus 2 female control hearts, and no statistical testing was done for cardiomyocyte data.
- Evident from the text: beta-blocker use was imbalanced (1 AD case vs. about one-third of controls), although ANOVA found no difference in diastolic function between control groups with and without beta-blocker therapy.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Claims the paper makes
5 Own result · 1 No full text of the sources
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Clinical assessment of myocardial function (Online Table 2) did not show any significant difference between AD cases and controls.”
§ Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer’s Disease > Results > Diastolic function is reduced in AD
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.
In the paper
“We found that age predicts a reduction in diastolic function by mitral valve E/A ratio (MVE/A) (Online Table 3A), as previously shown (28).”
§ Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer’s Disease > Results > Diastolic function is reduced in AD
What the sources say
- Not checked — no full text of the sourcecites [28] Nagueh, 2009, Recommendations for the evaluation of left ventricular diastolic function by echocardiography, J Am Soc Echocardiogr source
plaindirect- 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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The Student t-test analysis, as well as the estimates obtained by ordinary least squares of our linear regression model (Online Table 3B), showed no significant differences between AD and MVE/A ratio.”
§ Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer’s Disease > Results > Diastolic function is reduced in AD
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, diastolic function did not differ in the third tertiles of age in AD versus controls (MVE/A ratio 0.82 ± 0.08 vs. 0.86 ± 0.08).”
§ Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer’s Disease > Results > Diastolic function is reduced in AD
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, a correlation between AD and anticipated decline of myocardial function was present in the first age tertile (1.20 ± 0.18 vs. 1.34 ± 0.12) (Figure 1A).”
- Also stated in: § Anticipated diastolic dysfunction occurs in patients with clinical diagnosis of AD · plain
“we found that AD patients displayed worse values at younger ages compared with controls, asymptotically approaching the values of old-age controls”
§ Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer’s Disease > Results > Diastolic function is reduced in AD
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Anticipated diastolic dysfunction occurs in patients with clinical diagnosis of AD · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, we also used a linear regression F-test (p < 0.05), which showed that the pattern we observed was consistent with poorer diastolic function at earlier ages among the AD participants,”
§ Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer’s Disease > Results > Diastolic function is reduced in AD
hedgedcorrelational- 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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer’s Disease > Results > AD tissue samples
“a 70-year-old Caucasian woman with a clinical diagnosis of dementia. In this case, the clinical diagnosis of AD was confirmed at pathology”
§ Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer’s Disease > Limitations
“the diagnosis of 71-year-old case of AD followed the Aging-Alzheimer’s Association guidelines”
Citations
Cites
Oxidants, antioxidants, and the degenerative diseases of aging.
Ames, B. N., Shigenaga, M. K., & Hagen, T. M. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.7915 · Cited by 5,958
Amyloid plaque core protein in Alzheimer disease and Down syndrome.
Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.4245 · Cited by 4,431
Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography
Nagueh, S. F., Appleton, C. P., Gillebert, T. C., Marino, P. N., Oh, J. K., Smiseth, O. A., Waggoner, A. D., Flachskampf, F. A., Pellikka, P. A., & Evangelista, A. (2009) · Journal of the American Society of Echocardiography · doi:10.1016/j.echo.2008.11.023 · Cited by 4,367
Recommendations for the evaluation of left ventricular diastolic function by echocardiography
Nagueh, S. F., Appleton, C. P., Gillebert, T. C., Marino, P. N., Oh, J. K., Smiseth, O. A., Waggoner, A. D., Flachskampf, F. A., Pellikka, P. A., & Evangelisa, A. (2008) · European Journal of Echocardiography · doi:10.1093/ejechocard/jep007 · Cited by 3,351
Hyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092
Self-citationMontine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0910-3 · Cited by 2,894
Self-citationMolecular mechanism of Thioflavin-T binding to amyloid fibrils
Biancalana, M., & Koide, S. (2010) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2010.04.001 · Cited by 2,243
The Pathobiology of Vascular Dementia
Iadecola, C. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.008 · Cited by 1,857
Amyloid Precursor Protein Trafficking, Processing, and Function
Thinakaran, G., & Koo, E. H. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.r800019200 · Cited by 1,141
Demuro, A., Mina, E. W., Kayed, R., Milton, S. C. F., Parker, I., & Glabe, C. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500997200 · Cited by 1,057
Self-citation
Research works printed but not linked: 1
- Divry, 1927, Etude histochimique des plaques séniles, J Belge Neurol Psychiatr, 9, 649
Cited by
Sorted by citations
A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain
Wang, J., Gu, B. J., Masters, C. L., & Wang, Y.-J. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.111 · Cited by 808
Cardoso, A. L., Fernandes, A. M. A., Aguilar‐Pimentel, J. A., de Angelis, M. H., Guedes, J. R., Brito, M. A., Ortolano, S., Pani, G., Athanasopoulou, S., Gonos, E. S., et al. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.07.004 · Cited by 483
Alzheimer’s Disease and Vascular Aging
Cortes-Canteli, M., & Iadecola, C. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.10.062 · Cited by 400
Goette, A., Corradi, D., Dobrev, D., Aguinaga, L., Cabrera, J. Á., Chugh, S. S., de Groot, J. R., Soulat-Dufour, L., Fenelon, G., Hatem, S. N., et al. (2024) · EP Europace · doi:10.1093/europace/euae204 · Cited by 370
“17 Mechanistically, there is increasing evidence for the cardiotoxicity of soluble pre-amyloid oligomers.”
Vascular Cognitive Impairment (VCI)
Rundek, T., Tolea, M. I., Ariko, T., Fagerli, E. A., & Camargo, C. J. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01170-y · Cited by 347
“Elevated levels of Aβ in the heart and skeletal muscles of AD individuals indicate a possible contributor to elevated concentrations of Aβ plasma levels and potentially indirectly contributing to Aβ deposits in cerebral blood vessels and brain parenchyma [95].”
Background
Metadata
- Authors
- Troncone, L., Luciani, M., Coggins, M., Wilker, E. H., Ho, C.-Y., Codispoti, K. E., Frosch, M. P., Kayed, R., & del Monte, F.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Johns Hopkins University (US)
- Massachusetts General Hospital (US)
- The University of Texas Medical Branch at Galveston (US)
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 68
- Issue
- 22
- Pages
- 2395-2407
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC5142757
- OpenAlex
- W2558472983
- Cited by
- 204
- References
- 53
- Citations by year
- 2026: 18 · 2025: 30 · 2024: 27 · 2023: 22 · 2022: 15 · 2021: 24 · 2020: 21 · 2019: 13 · 2018: 11 · 2017: 20 · 2016: 3
- FWCI
- 12.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by-nc-nd)
- Funders
- American Heart Association (14IRG18980028, AHA 14IRG18980028)
- Società Italiana di Cardiologia
- National Institutes of Health (R01HL098468)
- National Heart, Lung, and Blood Institute (R01 HL098468, R21HL102716)
- 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
- Health Sciences › Medicine › Internal Medicine › Amyloidosis: Diagnosis, Treatment, Outcomes
- Keywords
- Alzheimer's disease, amyloid-beta, cardiac amyloidosis, heart failure, cardiac dysfunction, cardiomyocytes, calcium transients, cardiomyocyte shortening, systemic amyloidosis, multiple organ failure
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunohistochemistry, Male, Cardiomyopathies, Myocardium, Retrospective Studies, Immunoblotting, Amyloid beta-Peptides, Microscopy, Electron, Transmission
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