Alzheimer’s disease (AD) is a neurodegenerative disease that mainly affects people over 75 . Symptoms of AD include progressive memory loss and impaired cognitive function. AD involves fairly widespread brain atrophy, especially in a part of the temporal lobe called the hippocampus (23% reduction) , which seems to be involved in spatial memory and the consolidation of short term memory to long term memory. People with mild cognitive impairment (kind of like pre-AD) also have hippocampal atrophy (18% reduction) .
Mitochondrial Dysfunction in Alzheimer’s Disease
People with AD show several signs of mitochondrial dysfunction
- They have more mtDNA mutations than age-matched controls   , which was associated with an increase in amyloid-β and β-secretase activity 
- Many people with AD have specific mtDNA mutations that aren’t found in age-matched controls  
- They have a lower rate of glucose metabolism in various brain regions  . In addition healthy individuals with a maternal, but not paternal history of AD have a lower rate of glucose metabolism in cortex (mtDNA is maternally inherited) 
- Both people with AD and MCI have elevated levels of markers for oxidative stress in the central nervous system and the periphery. This may suggest that the source of oxidative stress is systemic  
- They have
lower levels of mitochondria and mitochondrial gene expression in the brain  
Mitochondrial Dysfunction as a Cause of Alzheimer’s Disease
There is some debate as to whether mitochondrial dysfunction is a cause or consequences of AD. The ‘Amyloid Cascade Hypothesis’ suggests amyloid-β is the cause of AD and that the mitochondrial dysfunction seen in AD is simply a consequence of amyloid-β toxicity . In addition, amyloid precursor protein has been found to accumulate in the mitochondria and impair their function . However, mitochondrial oxidative stress occurs early in AD and prior to amyloid-β toxicity . Oxidative stress increases amyloid precursor protein and amyloid-β, which is likely because amyloid-β seems to function as an antioxidant .
There is an animal model of AD (3xTg-AD mouse) where mitochondrial dysfunction is evident as early as 3 months of age and precedes AD-like pathology . There is also a very nice in vitro study that used cytoplasmic hybrid (cybrid) cell lines, which were developed from human neuroblastoma cells deficient in mtDNA and then repopulating them with mitochondria from either AD patients or age-latched controls. The cybrids with mitochondria from AD patients produced many AD-like pathologies, such as increased amyloid-β, oxidative stress and activation of apoptosis . The cybrid model allows this study to show that mitochondrial dysfunction can independently cause AD and is sufficient to cause the disease (at least in vitro)
The Mitochondria as a Therapeutic Target for Alzheimer’s Disease
Various strategies that stimulate mitochondrial biogenesis and/or promote oxidative phosphorylation appear to be somewhat therapeutic for AD
- A ketogenic diet improved verbal memory in people who have mild cognitive impairment 
- Calorie restriction (without changing micronutrient intake) reduced amyloid-β in the temporal lobe in an animal model of AD (Squirrel monkeys), which negatively correlated with the increase in Sirtuin-1 
- db/db mice are leptin resistant, insulin resistant and develop AD-like pathology and symptoms. Metformin reduced AD-like brain pathology, but didn’t reduce cognitive impairment 
- The combination of carnitine and lipoic acid improved memory in both old rats  and ApoE4 mice 
- Coenzyme Q10 reduced oxidative stress in the
brain, decreased Aβ levels and
improved cognitive performance in an animal model of AD (Tg19959 mice) 
The results of these studies aren’t as impressive as the studies in the Parkinson’s disease post. Two possible reasons are that: AD is a more complex disease than PD and mitochondrial dysfunction has a lesser role in AD; these therapies were given later in the disease progression and the degenerative nature of AD means it’s harder to recover if started off worse.