Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross‐PIA white paper that provides both a concise “state‐of‐the‐science” report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.

A large body of literature supports the idea that nuclear factor kappa B (NF-κB) signaling contributes to not only immunity, but also inflammation, cancer, and nervous system function. However, studies on NF-κB activity in mitochondrial function are much more limited and scattered throughout the literature. For example, in 2001 it was first published that NF-κB subunits were found in the mitochondria, including not only IkBα and NF-κB p65 subunits, but also NF-κB pathway proteins such as IKKα, IKKβ, and IKKγ, but not much follow-up work has been done to date. Upon further thought the lack of studies on NF-κB activity in mitochondrial function is surprising given the importance and the evolutionary history of both NF-κB and the mitochondrion. Both are ancient in their appearance in our biological record where both contribute substantially to cell survival, cell death, and the regulation of function and/or disease. Studies also show NF-κB can influence mitochondrial function from outside the mitochondria. Therefore, it is essential to understand the complexity of these roles both inside and out of this organelle. In this review, an attempt is made to understand how NF-κB activity contributes to overall mitochondrial function – both inside and out. The discussion at times is speculative and perhaps even provocative to some, since NF-κB does not yet have defined mitochondrial targeting sequences for some nuclear-encoded mitochondrial genes and mechanisms of mitochondrial import for NF-κB are not yet entirely understood. Also, the data associated with the mitochondrial localization of proteins must be yet further proved with additional experiments.

Mitochondria are the primary source for energy generation in the cell, which manifests itself in the form of the adenosine triphosphate (ATP). Nicotinamide dinucleotide (NADH) molecules are the first to enter the so-called electron transport chain or ETC of the mitochondria. The ETC represents a chain of reducing agents organized into four major protein-metal complexes (I-IV) that utilize the flow of electrons to drive the production of ATP. An additional integral protein that is related to oxidative phosphorylation is ATP synthase, referred to as complex V. Complex V carries out ATP synthesis as a result of the electron flow through the ETC. The coupling of electron flow from NADH to molecular oxygen to the production of ATP represents a process known as oxidative phosphorylation. In this review, we describe mainly the bioenergetic properties of mitochondria, such as those found in the ETC that may be altered in Alzheimer's disease (AD). Increasing evidence points to several mitochondrial functions that are affected in AD. Furthermore, it is becoming apparent that mitochondria are a potential target for treatment in early-stage AD. With growing interest in the mitochondria as a target for AD, it has been hypothesized that deficit in this organelle may be at the heart of the progression of AD itself. The role of mitochondria in AD may be significant and is emerging as a main area of AD research.