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.
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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.
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- Findingown data
Clinical assessment of myocardial function did not show any significant difference between AD cases and controls.
“Clinical assessment of myocardial function (Online Table 2) did not show any significant difference between AD cases and controls.”
Quote in the paperNot a substantial claim - Findingown data
Age predicts a reduction in diastolic function by mitral valve E/A ratio.
“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).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] Nagueh, 2009, Recommendations for the evaluation of left ventricular diastolic function by echocardiography, J Am Soc Echocardiogr source
- Findingown data
There were no significant differences between AD and MVE/A ratio in the overall analysis.
“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.”
Quote in the paperNot a substantial claim - Findingown data
Diastolic function did not differ in the third tertile of age in AD versus controls (MVE/A ratio 0.82 ± 0.08 vs. 0.86 ± 0.08).
“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).”
Quote in the paperNot a substantial claim - Findingown data
A correlation between AD and anticipated decline of myocardial function was present in the first age tertile (MVE/A 1.20 ± 0.18 vs. 1.34 ± 0.12).
“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”
Quote in the paperSubstantial claim - Also stated in: § Anticipated diastolic dysfunction occurs in patients with clinical diagnosis of AD · plain
- Findingown data
The pattern observed was consistent with poorer diastolic function at earlier ages among AD participants.
“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,”
Quote in the paperSubstantial claim
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.
Age of the pathologically confirmed case differs
MinorThe tissue-sample list identifies the pathologically confirmed AD case as 70 years old, but the limitations section refers to a 71-year-old case. No 71-year-old case appears in the list.
“a 70-year-old Caucasian woman with a clinical diagnosis of dementia. In this case, the clinical diagnosis of AD was confirmed at pathology”
“the diagnosis of 71-year-old case of AD followed the Aging-Alzheimer’s Association guidelines”
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Bulgart, H. R., Neczypor, E. W., Wold, L. E., & Mackos, A. R. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00378-4 · Cited by 116 · see citing works
“Soluble Aβ has been associated with decreased synaptic activity and weak nerve impulses, which suggests that Aβ contributes to synapse injury [15].”
BackgroundAmyloid-beta and tau protein beyond Alzheimer’s disease
Abyadeh, M., Gupta, V., Paulo, J. A., Mahmoudabad, A. G., Shadfar, S., Mirshahvaladi, S., Gupta, V. B., Nguyen, C. T. O., Finkelstein, D. I., You, Y., et al. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.386406 · Cited by 121 · see citing works
“Intriguingly, a retrospective cross-sectional study found the intramyocardial aggregates of Aβ 1–40 and Aβ 1–42 in AD patients, in addition, these patients showed diastolic dysfunction, suggesting AD as a systemic disease that may lead to failure of several organs (Troncone et al., 2016).”
BackgroundCardiac Contributions to Brain Health: A Scientific Statement From the American Heart Association
Testai, F. D., Gorelick, P. B., Chuang, P., Dai, X., Furie, K. L., Gottesman, R. F., Iturrizaga, J. C., Lazar, R. M., Russo, A. M., Seshadri, S. S., et al. (2024) · Stroke · doi:10.1161/str.0000000000000476 · Cited by 106 · see citing works
Alzheimer’s disease as type 3 diabetes: understanding the link and implications
Kciuk, M., Kruczkowska, W., Gałęziewska, J., Wanke, K., Kałuzińska-Kołat, Ż., Aleksandrowicz, M., & Kontek, R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252211955 · Cited by 98 · see citing works
Increased BACE1-AS long noncoding RNA and β-amyloid levels in heart failure
Greco, S., Zaccagnini, G., Fuschi, P., Voellenkle, C., Carrara, M., Sadeghi, I., Bearzi, C., Maimone, B., Castelvecchio, S., Stellos, K., et al. (2017) · Cardiovascular Research · doi:10.1093/cvr/cvx013 · Cited by 94 · see citing works
Ihara, M., & Washida, K. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170970 · Cited by 81 · see citing works
Ullah, R., Park, T. J., Huang, X., & Kim, M. O. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101451 · Cited by 78 · see citing works
“These contributing factors might explain the higher Aβ peptide deposition in the brain (central) than in peripheral organs (skin, intestinal tissues, subcutaneous tissue, and heart) (Joachim et al., 1989a; Koronyo et al., 2012; Troncone et al., 2016).”
Long Noncoding RNAs and Cardiac Disease
Greco, S., Salgado‐Somoza, A., Devaux, Y., & Martelli, F. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7126 · Cited by 70 · see citing works
Revisiting the role of brain and peripheral Aβ in the pathogenesis of Alzheimer's disease
Uddin, M. S., Kabir, M. T., Tewari, D., Mamun, A. A., Mathew, B., Aleya, L., Barreto, G. E., Bin-Jumah, M. N., Abdel‐Daim, M. M., & Ashraf, G. M. (2020) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2020.116974 · Cited by 68 · see citing works
Heart–brain axis in health and disease: role of innate and adaptive immunity
Simats, A., Sager, H. B., & Liesz, A. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae185 · Cited by 66 · see citing works
Roadmap for alleviating the manifestations of ageing in the cardiovascular system
Liberale, L., Tual-Chalot, S., Sedej, S., Ministrini, S., Georgiopoulos, G., Grunewald, M., Bäck, M., Bochaton-Piallat, M.-L., Boon, R. A., Ramos, G. C., et al. (2025) · Nature Reviews Cardiology · doi:10.1038/s41569-025-01130-5 · Cited by 59 · see citing works
Zhao, J.-K., Yu, L.-M., Xue, X., Xu, Y., Huang, T., Xu, D., Wang, Z.-S., Luo, L., & Wang, H.-S. (2023) · Redox Biology · doi:10.1016/j.redox.2022.102594 · Cited by 50 · see citing works
“Recent evidence suggests that Aβ deposits are also present in myocardium of AD patients and contributes to myocardial dysfunction [8], indicating that Aβ might play a potential role in AF.”
BackgroundGarofalo, M., Pandini, C., Bordoni, M., Pansarasa, O., Rey, F., Costa, A. C., Minafra, B., Diamanti, L., Zucca, S., Carelli, S., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249500 · Cited by 54 · see citing works
“Indeed, “dilated cardiomyopathy” has already been associated to heart failure in both AD, because of Aβ amyloid accumulation in the heart [41], and ALS, because of sympathetic hyperactivity that leads to cardiac death [42], which is the second cause of death in these patients.”
BackgroundElia, A., & Fossati, S. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1060666 · Cited by 52 · see citing works
“Indeed, we and other groups propose that HF itself may also be a result of cardiac Aβ accumulation triggered by AD pathology, which would instigate an accumulation of multiple amyloid proteins in an understudied potential vicious cycle between brain and heart deterioration (Troncone et al., 2016; Wang et al., 2017; Sa…”
BackgroundCardiac Abnormalities in Alzheimer Disease
Sanna, G. D., Nusdeo, G., Piras, M. R., Forteleoni, A., Murru, M. R., Saba, P. S., Dore, S., Sotgiu, G., Parodi, G., & Ganau, A. (2019) · JACC Heart Failure · doi:10.1016/j.jchf.2018.10.022 · Cited by 46 · see citing works
Interrelationship between Alzheimer’s disease and cardiac dysfunction: the brain–heart continuum?
Yang, M., Li, C., Zhang, Y., & Ren, J. T. (2019) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmz115 · Cited by 46 · see citing works
Luciani, M., Montalbano, M., Troncone, L., Bacchin, C., Uchida, K., Daniele, G., Wolf, B. J., Butler, H. M., Kiel, J., Berto, S., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad205 · Cited by 43 · see citing works
Self-citationAmyloid-Beta (1-40) Peptide and Subclinical Cardiovascular Disease
Stamatelopoulos, K. S., Pol, C. J., Ayers, C. R., Georgiopoulos, G. A., Gatsiou, A., Brilakis, E. S., Khera, A., Drosatos, K., de Lemos, J. A., & Stellos, K. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.06.027 · Cited by 42 · see citing works
On the Role of Platelet-Generated Amyloid Beta Peptides in Certain Amyloidosis Health Complications
Inyushin, M. Y., Zayas‐Santiago, A., Rojas, L. V., & Kucheryavykh, L. Y. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.571083 · Cited by 41 · see citing works
Badhwar, A., Hirschberg, Y., Valle‐Tamayo, N., Iulita, M. F., Udeh‐Momoh, C. T., Matton, A., Tarawneh, R. M., Rissman, R. A., Ledreux, A., Winston, C. N., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13823 · Cited by 34 · see citing works
Amyloid-β and heart failure in Alzheimer’s disease: the new vistas
Al-kuraishy, H., Sulaiman, G., Mohammed, H. A., Mohammed, S. G., Al-Gareeb, A., Albuhadily, A. K., Dawood, R. A., Ali, A. A., & Abu-Alghayth, M. H. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1494101 · Cited by 43 · see citing works
The Brain–Heart Axis: Alzheimer’s, Diabetes, and Hypertension
Riching, A. S., Major, J. L., Londono, P., & Bagchi, R. A. (2019) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.9b00091 · Cited by 37 · see citing works
Age-related amyloidosis outside the brain: A state-of-the-art review
Tasaki, M., Lavatelli, F., Obici, L. P., Obayashi, K., Miyamoto, T. K., Merlini, G., Palladini, G. O., Ando, Y., & Ueda, M. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101388 · Cited by 34 · see citing works
Gagno, G., Ferro, F., Fluca, A. L., Janjusevic, M., Rossi, M., Sinagra, G., Beltrami, A. P., Moretti, R., & Aleksova, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249655 · Cited by 36 · see citing works
Plasma Amyloid-β in Relation to Cardiac Function and Risk of Heart Failure in General Population
Zhu, F., Wolters, F. J., Yaqub, A., Leening, M. J. G., Ghanbari, M., Boersma, E. H., Ikram, M. A., & Kavousi, M. (2022) · JACC Heart Failure · doi:10.1016/j.jchf.2022.09.006 · Cited by 33 · see citing works
Ettcheto, M., Sánchez‐López, E., Gómez-Mínguez, Y., Cabrera, H., Busquets, O., Beas‐Zárate, C., García, M. L., Carro, E., Casadesús, G., Auladell, C., et al. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0868-4 · Cited by 32 · see citing works
Priming the Proteasome to Protect against Proteotoxicity
Wang, X., & Wang, H. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.02.007 · Cited by 32 · see citing works
Heuschkel, M. A., Skenteris, N. T., Hutcheson, J. D., van der Valk, D. C., Bremer, J., Goody, P. R., Hjortnaes, J., Jansen, F., Bouten, C. V. C., van den Bogaerdt, A., et al. (2020) · Cells · doi:10.3390/cells9102164 · Cited by 32 · see citing works
Jabeen, K., Rehman, K., & Akash, M. S. H. (2021) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.22953 · Cited by 32 · see citing works
Interactions between nanoparticles and pathological changes of vascular in Alzheimer’s disease
Lei, T., Yang, Z., Li, H., Qin, M., & Gao, H. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115219 · Cited by 32 · see citing works
The long and winding road to target protein misfolding in cardiovascular diseases
Diteepeng, T., Monte, F., & Luciani, M. (2021) · European Journal of Clinical Investigation · doi:10.1111/eci.13504 · Cited by 22 · see citing works
Self-citationBeta-Amyloid Instigates Dysfunction of Mitochondria in Cardiac Cells
Jang, S., Chapa‐Dubocq, X. R., Parodi‐Rullán, R. M., Fossati, S., & Javadov, S. A. (2022) · Cells · doi:10.3390/cells11030373 · Cited by 30 · see citing works
AβPeptide Originated from Platelets Promises New Strategy in Anti-Alzheimer’s Drug Development
Inyushin, M. Y., Sanabria, P., Rojas, L. V., Kucheryavykh, Y. V., & Kucheryavykh, L. Y. (2017) · BioMed Research International · doi:10.1155/2017/3948360 · Cited by 30 · see citing works
“As proposed by others [68], AD may be viewed either as a systemic disease or as a metastatic disorder, possibly leading to multiple organ failure.”
BackgroundPan, B., Lewno, M. T., Wu, P., & Wang, X. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00758 · Cited by 29 · see citing works
“The activation of TFEB has been shown to stimulate ALP function, which enhances the clearance of misfolded or aggregation-prone proteins both in cellular models of protein misfolding and mouse models of neurodegenerative disease (Dehay et al., 2010; Tsunemi et al., 2012; Decressac et al., 2013).”
BackgroundPeripheral proteinopathy in neurodegenerative diseases
Xu, B., Lei, X., Yang, Y., Yu, J., Chen, J., Xu, Z., Ye, K., & Zhang, J. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-024-00461-6 · Cited by 30 · see citing works
Mortality From Heart Failure and Dementia in the United States: CDC WONDER 1999–2016
Vuong, J. T., Jacob, S., Alexander, K. M., Singh, A., Liao, R., Desai, A. S., & Dorbala, S. (2018) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2018.11.012 · Cited by 28 · see citing works
Reduced Cardiovascular Functions in Patients with Alzheimer’s Disease
Jin, W.-S., Bu, X.-L., Wang, Y.-R., Li, L., Li, W.-W., Liu, Y.-H., Zhu, C., Yao, X.-Q., Chen, Y., Gao, C.-Y., et al. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-170088 · Cited by 27 · see citing works
Is It the Twilight of BACE1 Inhibitors?
Hrabinova, M., Pejchal, J., Kucera, T., Jun, D., Schmidt, M., & Soukup, O. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666200503023323 · Cited by 28 · see citing works
“It is noteworthy that Aβ1-40 and Aβ1-42 are expressed in the heart of AD patients, and compounds showing anti-BACE-1 activity and no hERG affinity may prevent heart failure [127, 128].”
BackgroundA Healthy Heart and a Healthy Brain: Looking at Mitophagy
Luo, H., Zhang, R., Krigman, J., McAdams, A., Ozgen, S., & Sun, N. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00294 · Cited by 25 · see citing works
“And recent studies have demonstrated compromised myocardial function and intramyocardial deposits of Aβ in AD patients (Troncone et al., 2016).”
BackgroundHeart and Brain: Complex Relationships for Left Ventricular Dysfunction
Daniele, G., DiLucia, S., Masci, P. G., & del Monte, F. (2020) · Current Cardiology Reports · doi:10.1007/s11886-020-01318-w · Cited by 27 · see citing works
Bloodstream Amyloid-beta (1-40) Peptide, Cognition, and Outcomes in Heart Failure
Antoni Bayes-genis, A., Barallat, J., de Antonio, M., Domingo, M., Zamora, E., Vila, J., Subirana, I., Gastelurrutia, P., Pastor, M. C., Januzzi, J. L., et al. (2017) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2017.02.021 · Cited by 25 · see citing works
“Amyloid-beta 1- 40 peptide is recognized as a proinflammatory peptide that acts through several mechanisms.9 In normal metabolism, Ab40 is removed from the brain by multiple processes, including degradation by NEP.10 While circulating concentrations of Ab40 have been linked with subclinical atherosclerosis and progres…”
BackgroundInfluentialMuntsant-Soria, A., Jiménez‐Altayó, F., Puertas-Umbert, L., Jiménez‐Xarrié, E., Vila, E., & Giménez‐Llort, L. (2021) · Biomedicines · doi:10.3390/biomedicines9020111 · Cited by 24 · see citing works
“Thus, amyloid pathology affects patients’ hearts [16], and the impact of cerebrovascular dysfunction independently of cerebral amyloid angiopathy has also been demonstrated [17].”
BackgroundČermáková, P., Muller, M., Armstrong, A. D. C., Religa, D., Bryan, R. N., Lima, J. A. C., & Launer, L. J. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.006750 · Cited by 24 · see citing works
The Heart-Brain-Metabolism Axis in Cardiovascular and Neurologic Disease
Tardo, D. T., Cortés‐Canteli, M., Fuster, V., Sachdev, P. S., & Kovacic, J. C. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2025.09.1602 · Cited by 33 · see citing works
Cao, C., Hasegawa, Y., Hayashi, K., Takemoto, Y., & Kim‐Mitsuyama, S. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-181000 · Cited by 23 · see citing works
Tetrameric Transthyretin as a Protective Factor Against Alzheimer’s Disease
Corino, C., Aimo, A., Luigetti, M., Ciccone, L., Chen, Y. F. F., Panichella, G., Musetti, V., Castiglione, V., Vergaro, G., Emdin, M., et al. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04442-8 · Cited by 21 · see citing works
Current and future circulating biomarkers for cardiac amyloidosis
Luciani, M., Troncone, L., & del Monte, F. (2018) · Acta Pharmacologica Sinica · doi:10.1038/aps.2018.38 · Cited by 20 · see citing works
Self-citationEXOSOME RELEASE AND CARGO IN DOWN SYNDROME
Hamlett, E., Larosa, A. C., Mufson, E., Fortea, J., Ledreux, A., & Granholm, A. (2019) · Developmental Neurobiology · doi:10.1002/dneu.22712 · Cited by 21 · see citing works
“Additionally, it has been discovered that Aβ aggregates are present in the myocardium of patients with AD (Troncone et al., 2016).”
BackgroundLiao, R., & Ward, J. E. (2017) · Circulation Research · doi:10.1161/circresaha.117.310643 · Cited by 21 · see citing works
“Even in diseases thought to be localized, such as Alzheimer disease, APP (amyloid β precursor protein)-derived Aβ protein has been found in the heart.(9) With over 10% of the population over the age of 65 years currently experiencing Alzheimer disease and only expected to increase, the potential rise in cardiac amyloi…”
BackgroundDoes protein aggregation drive postmitotic tissue degeneration?
Kelly, J. W. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.aax0914 · Cited by 20 · see citing works
“Several groups have demonstrated that some patients with AD have subclinical heart disease, including diastolic and myocardial dysfunction, apparently caused by A aggregate deposition in the cardiomyocytes and interstitium (34, 35).”
BackgroundAmyloid-β: A potential mediator of aging-related vascular pathologies
Khan, F., & Qiu, H. (2023) · Vascular Pharmacology · doi:10.1016/j.vph.2023.107213 · Cited by 21 · see citing works
Alaaeddine, R. A., Fayad, M., Nehme, E., Bahmad, H. F., & Kobeissy, F. H. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-60733-7_4 · Cited by 20 · see citing works
Amyloid Beta Peptide Is Released during Thrombosis in the Skin
Kucheryavykh, L. Y., Kucheryavykh, Y. V., Washington, A. V., & Inyushin, M. Y. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061705 · Cited by 20 · see citing works
Heart Failure in Older Patients: An Update
Montalto, M., D’Ignazio, F., Camilli, S., Francesco, S. D., Fedele, M., Landi, F., & Gallo, A. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14061982 · Cited by 24 · see citing works
“For example, intramyocardial deposits of amyloid-β 40 and β 42, commonly seen in neurodegeneration, as well as in diastolic dysfunction, have been observed in AD patients with HF [38].”
Increased Levels of Coagulation Factor XI in Plasma Are Related to Alzheimer’s Disease Diagnosis
Begić, E., Hadžidedić, S., Obradovic, S. D., Begić, Z., & Čaušević, M. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200358 · Cited by 19 · see citing works
Hsieh, M., Chen, D., Lee, C., Wu, C.-L., Chen, Y.-J., Huang, Y., & Chang, S. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.831730 · Cited by 19 · see citing works
“The hallmark feature of AD, the accumulation of beta-amyloid proteins in the extracellular space of the brain, can also be found in the left ventricle (34).”
BackgroundTargeting Prion-like Cis Phosphorylated Tau Pathology in Neurodegenerative Diseases
Albayram, Ö., Angeli, P. A., Bernstein, E. R., Baxley, S., Gao, Z. J., Lu, K. P., & Zhou, X. Z. (2018) · Journal of Alzheimer’s Disease & Parkinsonism · doi:10.4172/2161-0460.1000443 · Cited by 19 · see citing works
“Pin1, a peptidyl-prolyl cis-trans isomerase, binds to phosphorylated tau primarily at the Thr231 residue, catalyzing the conversion from cis to trans p-tau at that site [32-43] (Figure 1).”
Baranowski, B. J., Allen, M. D., Nyarko, J. N. K., Rector, R. S., Padilla, J., Mousseau, D. D., Rau, C. D., Wang, Y., Laughlin, M. H., Emter, C. A., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.143141 · Cited by 18 · see citing works
Li, J., Zhang, Y., You, Y., Huang, Z., Wu, L., Liang, C., Weng, B., Pan, L., Huang, Y., Huang, Y., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1360687 · Cited by 18 · see citing works
Aishwarya, R., Abdullah, C. S., Remex, N. S., Bhuiyan, M. A. N., Lu, X., Dhanesha, N., Stokes, K. Y., Orr, A. W., Kevil, C. G., & Bhuiyan, M. S. (2024) · Scientific Reports · doi:10.1038/s41598-024-67638-x · Cited by 18 · see citing works
“Additionally, APP SWE /PS1 Tg hearts also displayed ubiquitous non-uniform deposition of Aβ aggregates in the myocardium, correlating with intramyocardial deposition of amyloid aggregates observed in AD hearts 35,54 .”
BackgroundInfluentialRole of circulating factors in cardiac aging
Cannata, A. N., Marcon, G., Cimmino, G., Camparini, L., Ciucci, G., Sinagra, G., & Loffredo, F. S. (2017) · Journal of Thoracic Disease · doi:10.21037/jtd.2017.03.95 · Cited by 19 · see citing works
“Persistent activation of RAAS also stimulates β-amiloid production (112), an important link between cardiac and neuronal aging (113).”
BackgroundShityakov, S., Hayashi, K., Störk, S., Scheper, V., Lenarz, T., & Förster, C. Y. (2021) · Biomolecules · doi:10.3390/biom11060900 · Cited by 18 · see citing works
Raisi‐Estabragh, Z., M'Charrak, A., McCracken, C., Biasiolli, L., Ardissino, M., Curtis, E. M., Aung, N., Suemoto, C. K., Mackay, C. E., Suri, S., et al. (2021) · European Heart Journal - Cardiovascular Imaging · doi:10.1093/ehjci/jeab075 · Cited by 17 · see citing works
“Two other cohort studies demonstrate greater prevalence of diastolic dysfunction (assessed by echocardiography) in individuals with Alzheimer’s disease compared with controls.(32,33) Limited studies have examined associations with other cardiovascular phenotypes.”
Luo, M., Pang, Y., Li, J., Yi, L., Wu, B., Tian, Q., He, Y., Wang, M., Xia, L., He, G., et al. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.10.015 · Cited by 17 · see citing works
Amyloid-beta metabolism in age-related neurocardiovascular diseases
Aivalioti, E., Georgiopoulos, G. A., Tual‐Chalot, S., Bampatsias, D., Delialis, D., Sopova, K., Drakos, S. G., Stellos, K., & Stamatelopoulos, K. S. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae655 · Cited by 19 · see citing works
“5,68,107,108 Amyloid-beta pathology is triggered by ageing, environmental factors, and genomic traits.”
Atrial fibrillation and Alzheimer’s disease: A conundrum
Benenati, S., Canale, C., Marzo, V. D., Bona, R. D., Rosa, G. M., & Porto, I. (2020) · European Journal of Clinical Investigation · doi:10.1111/eci.13451 · Cited by 17 · see citing works
The Heart of the Alzheimer's: A Mindful View of Heart Disease
Evangelisti, A., Butler, H. M., & del Monte, F. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2020.625974 · Cited by 17 · see citing works
Clinical and Imaging Markers of Cardiac Function and Brain Health
Yaqub, A., Bis, J. C., Frenzel, S., Koini, M., Mbangdadji, D., Peloso, G. M., Talluri, R., Alonso, Á., Bahls, M., Bülow, R., et al. (2025) · Neurology · doi:10.1212/wnl.0000000000213421 · Cited by 16 · see citing works
Perrone, L., & Valente, M. (2021) · Biomolecules · doi:10.3390/biom11111652 · Cited by 16 · see citing works
Yu, H., Wang, M., Yang, Q., Xu, X., Zhang, R., Chen, X., & Le, W. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12853 · Cited by 16 · see citing works
Amiloide beta (1-40) en sangre, cognición y pronóstico en insuficiencia cardiaca
Antoni Bayes-genis, A., Barallat, J., de Antonio, M., Domingo, M., Zamora, E., Vila, J., Subirana, I., Gastelurrutia, P., Pastor, M. C., Januzzi, J. L., et al. (2017) · Revista Española de Cardiología · doi:10.1016/j.recesp.2017.02.006 · Cited by 16 · see citing works
“Las de Ab40 tendieron a ser superiores en los pacientes con fibrilación auricular (mediana, 564,0 [384,7796,2]) en comparación con los que estaban en ritmo sinusal (500,6 [354,2-736,3]; p = 0,056), y hubo más pacientes con fibrilación auricular que tenı́an concentraciones de Ab40 superiores a la mediana (tabla 1).”
BackgroundInfluentialEsfandiarei, M., Hoxha, B., Talley, N., Anderson, M., Alkhouli, M. F., Squire, M., Eckman, D. M., Babu, J. R., Lopaschuk, G. D., & Broderick, T. L. (2019) · Drug Design Development and Therapy · doi:10.2147/dddt.s196119 · Cited by 16 · see citing works
Cyr, B. S., Ranaldi, E. D. L. R. M. C., Hadad, R., Dietrich, W. D., Keane, R. W., & Vaccari, J. P. D. R. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1369781 · Cited by 15 · see citing works
Investigating the Interplay between Cardiovascular and Neurodegenerative Disease
Cousineau, J., Dawe, A. M., & Alpaugh, M. (2024) · Biology · doi:10.3390/biology13100764 · Cited by 15 · see citing works
“Furthermore, amyloid-beta aggregates have been identified within cardiomyocytes, disrupting Ca 2+ homeostasis and contributing to myocardial dysfunction [49,50].”
BackgroundFluca, A. L., Pani, B., Janjusevic, M., Zwas, D. R., Abraham, Y., Calligaris, M., Beltrami, A. P., Corgosinho, F. C., Marketou, M. E., D’Errico, S., et al. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.122911 · Cited by 14 · see citing works
Suryadevara, V., Klüppel, M., del Monte, F., & Willis, M. S. (2020) · American Journal Of Pathology · doi:10.1016/j.ajpath.2020.04.013 · Cited by 13 · see citing works
Pathophysiological pathways in patients with heart failure and atrial fibrillation
Santema, B. T., Arita, V. A., Sama, I. E., Kloosterman, M., van den Berg, M. P., Nienhuis, H. L. A., Gelder, I. C. V., van der Meer, P., Zannad, F. M., Metra, M., et al. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab331 · Cited by 14 · see citing works
“Suggesting a unifying pathogenesis, Troncone et al.(34) performed a cross-sectional study investigating cardiac involvement of patients with a primary diagnosis of Alzheimer’s disease as compared to age-matched controls.”
BackgroundResultJu, D., Huang, R.-F. S., Tsai, B. C., Su, Y.-C., Chiu, P., Chang, Y., Padma, V. V., Ho, T., Yao, C., Kuo, W., et al. (2023) · Neurotoxicity Research · doi:10.1007/s12640-023-00666-z · Cited by 14 · see citing works
“Some studies have indicated an association between Alzheimer's disease and the risk of heart-related issues, such as arrhythmias, heart failure, and myocardial infarction (Tolppanen et al. 2013; Troncone et al. 2016; Zulli et al. 2008).”
BackgroundAmyloidosis of the Brain and Heart
Schaich, C. L., Maurer, M. S., & Nadkarni, N. K. (2019) · JACC Heart Failure · doi:10.1016/j.jchf.2018.12.014 · Cited by 14 · see citing works
“al (6) clearly demonstrate, albeit in a small population, that Aβ fragments are present in the hearts of patients with AD, but are at much lower concentrations than that seen in the brain in AD.”
BackgroundDo Neurotrophins Connect Neurological Disorders and Heart Diseases?
Fujitani, M., Otani, Y., & Miyajima, H. (2021) · Biomolecules · doi:10.3390/biom11111730 · Cited by 13 · see citing works
Oxysterols in Central and Peripheral Synaptic Communication
Petrov, A. M. (2023) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-43883-7_6 · Cited by 13 · see citing works
Nailfold Capillary Morphology in Alzheimer’s Disease Dementia
Cousins, C. C., Alosco, M. L., Cousins, H. C., Chua, A. S., Steinberg, E. G., Chapman, K. R., Bing‐Canar, H., Tripodis, Y., Knepper, P. A., Stern, R. A., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180658 · Cited by 13 · see citing works
Is heart failure with preserved ejection fraction a ‘dementia’ of the heart?
Tini, G., Cannata, A. N., Canepa, M., Masci, P. G., Pardini, M., Giacca, M., Sinagra, G., Marchionni, N., del Monte, F., Udelson, J. E., et al. (2021) · Heart Failure Reviews · doi:10.1007/s10741-021-10114-9 · Cited by 13 · see citing works
Ettcheto, M., Sánchez‐López, E., Cano, A. C., Carrasco, M., Herrera, K., Manzine, P. R., Espinosa-Jiménez, T., Busquets, O., Verdaguer, E., Olloquequi, J., et al. (2021) · Cell & Bioscience · doi:10.1186/s13578-021-00646-w · Cited by 12 · see citing works
Differential associations between retinal signs and CMBs by location
Qiu, C., Ding, J., Sigurdsson, S. O., Fisher, D. E., Zhang, Q., Eiríksdóttir, G., Klein, R., van Buchem, M. A., Gudnason, V. G., Cotch, M. F., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000004792 · Cited by 12 · see citing works
- 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
- Health Sciences › Medicine › Physiology › 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 › 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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