# Mitochondrial connection to Alzheimer’s disease and heart failure

**Authors:** Anupriya Sinha, Natasha Jaiswal, Pooja Jadiya, Dhanendra Tomar

PMC · DOI: 10.1016/j.cophys.2025.100830 · Current opinion in physiology · 2026-04-01

## TL;DR

This paper explores how mitochondrial dysfunction connects Alzheimer's disease and heart failure, suggesting mitochondria-targeted therapies could treat both.

## Contribution

The paper highlights mitochondrial dysfunction as a shared mechanism linking Alzheimer's disease and cardiovascular diseases.

## Key findings

- Mitochondrial dysfunction disrupts energy production and oxidative balance in both Alzheimer's and heart failure.
- There is a bidirectional relationship between brain and heart health through mitochondrial pathways.
- Targeting mitochondria could lead to new therapies for both neurodegenerative and cardiovascular diseases.

## Abstract

The brain and heart are intricately linked, with dysfunction in one organ often affecting the other. Cardiovascular diseases (CVDs), particularly heart failure, impair cerebral blood flow, contributing to cognitive decline and increasing dementia risk. Conversely, Alzheimer’s disease (AD), marked by amyloid-beta plaques and tau tangles, impacts cardiac function. A shared mechanism between AD and CVDs is mitochondrial dysfunction, which disrupts energy production and oxidative balance, worsening both neurodegeneration and heart health. This interdependence underscores the potential for mitochondria-targeted therapies to address both conditions. With an aging population facing rising incidences of AD and CVDs, understanding these interconnected pathways and the central role of mitochondria could inform new therapeutic strategies and improve outcomes in both neurodegenerative and cardiovascular diseases.

## Linked entities

- **Diseases:** Alzheimer’s disease (MONDO:0004975), heart failure (MONDO:0005252), dementia (MONDO:0001627)

## Full-text entities

- **Genes:** DES (desmin) [NCBI Gene 1674] {aka CDCD3, CSM1, CSM2, LGMD1D, LGMD1E, LGMD2R}, PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1) [NCBI Gene 5564] {aka AMPK, HAMPKb}, PSEN2 (presenilin 2) [NCBI Gene 5664] {aka AD3L, AD4, CMD1V, PS2, STM2}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, IAPP (islet amyloid polypeptide) [NCBI Gene 3375] {aka DAP, IAP}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, PSEN1 (presenilin 1) [NCBI Gene 5663] {aka ACNINV3, AD3, CMD1U, FAD, PS-1, PS1}, DNM1L (dynamin 1 like) [NCBI Gene 10059] {aka DLP1, DRP1, DVLP, DYMPLE, EMPF, EMPF1}, MAVS (mitochondrial antiviral signaling protein) [NCBI Gene 57506] {aka CARDIF, IPS-1, IPS1, VISA}
- **Diseases:** diastolic dysfunction (MESH:D018487), mitochondrial defects (MESH:C565376), Inflammatory (MESH:D007249), cardiac arrhythmia (MESH:D001145), mitochondrial energy failure (MESH:D051437), endothelial dysfunction (MESH:D014652), neuronal damage (MESH:D009410), cerebral amyloid angiopathy (MESH:D016657), cardiac abnormalities (MESH:D018376), AD (MESH:D000544), hypertension (MESH:D006973), cardiac and neurological deterioration (MESH:D009461), amyloid (MESH:C000718787), heart failure (MESH:D006333), Calcium (MESH:D002128), pathologies (MESH:D005598), HCM (MESH:D002312), brain disorders (MESH:D001927), brain atrophy (MESH:C566985), cerebral hypoperfusion (MESH:D002547), dementia (MESH:D003704), mitochondrial fragmentation (MESH:D012892), AF (MESH:D001281), impaired heart muscle contraction (MESH:D009135), ischemic (MESH:D002545), cardiac and neurodegenerative disorders (MESH:D019636), neurological deterioration (MESH:D009422), ischemia (MESH:D007511), cardiomyopathies (MESH:D009202), atherosclerosis (MESH:D050197), reperfusion injury (MESH:D015427), diabetes (MESH:D003920), Mitochondrial dysfunction (MESH:D028361), neuroinflammation (MESH:D000090862), Cognitive decline (MESH:D003072), dilated (MESH:D002311), energy deficiency (MESH:D011502), CVD (MESH:D002318), toxicity (MESH:D064420), metabolic insufficiency (MESH:D000309), mitochondrial overload (MESH:D019190), obesity (MESH:D009765), cardiomyocyte death (MESH:D003643), demyelination (MESH:D003711), Cardiac dysfunction (MESH:D006331), atrophy (MESH:D001284), neurofibrillary (MESH:D055956), insulin resistance (MESH:D007333), metabolic dysregulation (MESH:D021081), complex I and complex IV of (MESH:D030401), synaptic loss (MESH:D012183), stroke (MESH:D020521), acidosis (MESH:D000138)
- **Chemicals:** Metformin (MESH:D008687), ATP (MESH:D000255), acetylcholine (MESH:D000109), ROS (MESH:D017382), lipid (MESH:D008055), oxygen (MESH:D010100), cholesterol (MESH:D002784), calcium (MESH:D002118)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC13037930/full.md

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13037930/full.md

## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC13037930/full.md

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Source: https://tomesphere.com/paper/PMC13037930