Student ID: 170438647
Word count: 999
, Mitochondria are the major key molecules in the pathogenesis of Alzheimer’s Disease.
Alzheimer’s Disease (AD) is the most common form of dementia and the exact aetiology has
yet to be discovered. Several findings are pointing at an apparent mitochondrial dysfunction
being involved in the generation of the hallmarks of AD, in neurotransmission disruption and
increased risk of developing AD. Additionally, non-pharmacological treatments aiming to
reduce oxidative stress show neuroprotective effects in AD. Since there is some controversy
on whether mitochondria impairment drives amyloid β (Aβ) formation and tau
phosphorylation or vice versa, the confidence of mitochondria being a key player in the
pathogenesis of AD is 7/10.
AD is mostly a disease of the elderly and a common impairment seen in the ageing
population is that of mitochondria. Indeed, as we get old mitochondria undergo a decline in
their respiratory capacity and an increase in reactive oxygen species (ROS) 1.
Surprisingly, the dysfunction in mitochondria characteristic of people with sporadic AD
seems to happen long before the Aβ plaques and NFT formation and probably it accounts
for the downstream pathological cascade observed in AD2,3.
Despite the conflicting evidence, several studies have supported the idea of mitochondria
dysfunction being responsible for the processing of amyloid precursor protein (APP) towards
and amyloidogenic fate and mitochondrial deoxyribonucleic acid (mtDNA) mutations
enhancing amyloid plaques aggregation4.
For instance, inhibition of the enzyme cytochrome c oxidase (COX) in cell culture
experiments altered the processing of APP towards an amyloidogenic profile 5. It is important
to mention that COX activity, which is ultimately important in the production of adenosine
triphosphate, is known to be reduced in AD-derived platelets6.
However, a more recent study has suggested that mitochondrion-derived ROS may be
enough on their own to drive the amyloidogenic processing of APP 7.
Regarding the other hallmark of AD, namely phosphorylated tau, there is evidence of
mitochondria-induced oxidative stress affecting downstream targets such as glycogen
synthase kinase 3 beta which ultimately increase tau phosphorylation levels. Altered levels
of tau phosphorylation create a pathological feedback loop with mitochondria which will
eventually affect synaptic formation8,9.
Word count: 999
, Mitochondria are the major key molecules in the pathogenesis of Alzheimer’s Disease.
Alzheimer’s Disease (AD) is the most common form of dementia and the exact aetiology has
yet to be discovered. Several findings are pointing at an apparent mitochondrial dysfunction
being involved in the generation of the hallmarks of AD, in neurotransmission disruption and
increased risk of developing AD. Additionally, non-pharmacological treatments aiming to
reduce oxidative stress show neuroprotective effects in AD. Since there is some controversy
on whether mitochondria impairment drives amyloid β (Aβ) formation and tau
phosphorylation or vice versa, the confidence of mitochondria being a key player in the
pathogenesis of AD is 7/10.
AD is mostly a disease of the elderly and a common impairment seen in the ageing
population is that of mitochondria. Indeed, as we get old mitochondria undergo a decline in
their respiratory capacity and an increase in reactive oxygen species (ROS) 1.
Surprisingly, the dysfunction in mitochondria characteristic of people with sporadic AD
seems to happen long before the Aβ plaques and NFT formation and probably it accounts
for the downstream pathological cascade observed in AD2,3.
Despite the conflicting evidence, several studies have supported the idea of mitochondria
dysfunction being responsible for the processing of amyloid precursor protein (APP) towards
and amyloidogenic fate and mitochondrial deoxyribonucleic acid (mtDNA) mutations
enhancing amyloid plaques aggregation4.
For instance, inhibition of the enzyme cytochrome c oxidase (COX) in cell culture
experiments altered the processing of APP towards an amyloidogenic profile 5. It is important
to mention that COX activity, which is ultimately important in the production of adenosine
triphosphate, is known to be reduced in AD-derived platelets6.
However, a more recent study has suggested that mitochondrion-derived ROS may be
enough on their own to drive the amyloidogenic processing of APP 7.
Regarding the other hallmark of AD, namely phosphorylated tau, there is evidence of
mitochondria-induced oxidative stress affecting downstream targets such as glycogen
synthase kinase 3 beta which ultimately increase tau phosphorylation levels. Altered levels
of tau phosphorylation create a pathological feedback loop with mitochondria which will
eventually affect synaptic formation8,9.
