Alzheimer’sdisease (AD) and Parkinson’s disease (PD) are both central nervous system and agerelated neurodegenerative diseases characterized by slowly progressive loss onneurons (Gandhi& Abramov 2012). AD is a progressive neurologic disease thatresults in the irreversible loss of neurons, in the cortex and hippocampuscharacterized by progressive cognitive decline. Two major pathologicalhallmarks of AD are accumulation beta Amyloid- A? peptide andhyper-phosphorylation of tau (Xie, Gao, Xu & Megn, 2014).
On the otherhand,Pathologically, PD is highlighted by degeneration of dopamine neurons in thesubstantia nigra pars compacta and the aggregation of a-synuclein protein inLewy body inclusion in the brain. Symptoms that characterize PD includetremors, rigidity and slower movement (Xie, Gao, Xu & Megn, 2014). AlthoughAD and PD have distinct mechanisms of etiology, different brain regions anddistinct clinical features, A multitude of research points to the possibilityof a pathologic overlap between the two disorders, especially in thedevelopment of neurodegeneration.
Therefore, the aim of this essay is todiscuss the evidence that while PD and AD are distinct neurological disordersthere are some similarities as well as some differences in the underlyingbiological mechanisms of these disorders. A commonpathological mechanism of AD and PD is the accumulation of the altered protein suggestinga common pathway for this two neurodegenerative disorders. However, the proteininvolved in each is different, AD is characterized by insoluble protein depositof A? plaques and tau- containing neurofibrillary lesions; and a-synuclein containing Lewy bodies in PD. A multitude of research, suggest thataccumulation of disposal A? are the primary cause of AD, this is called theamyloid hypothesis. According to the amyloid hypothesis stages of A?aggregation disrupt cell communication and activate immune cells, this cellstrigger inflammation therefore the brain cells are destroyed (Hardy et al.,2014). Different lines of evidence support the amyloidhypothesis. Genetic studies provide the strongest evidence and emphasize therole of A? as a key initiator of the disease.
It was discovered that familialAD was caused by mutation of APP gene or mutation in the presenilin 1 and 2which are involved in cutting A? from APP. Also individuals with down syndromewho have three copies of the chromosome carrying the APP almost always developamyloid plaques by the age of forty. Brouillette et al, (2012) developed a newin vivo technique to investigate the effects of small, soluble A?1– 42 oligomers. One week after Bilateral cannulae were implanted in the DG, freelymoving and awake mice received hippocampal injections of soluble A?42 oligomers and vehicle every dayfor six days, mice than were killed 24 hours after they received their lastinjection. It was observed that A?1– 42 oligomers had accumulated in the DG andneuronal death was observed in the surrounding areas of oligomer deposition. Todetermine the role of toxic A?1– 42 oligomers which had accumulated for three andsix days the authors further performed a hippocampal protein extraction.
Similar amounts of the different A?1– 42 oligomers were obtained 3 and 6 days afterinjections suggesting that A? oligomers accumulated at the level of cellbodies. Importantly cell death was not only observed in the dorsal hippocampusbut also in the ventral part of the hippocampus. While pathogenesis of AD isexplained by the amyloid hypothesis, Hasegawa et al (2016) argued that althoughthe association between amyloid plaques and AD is evident, treatment with antiA? antibodies does not always ease symptoms in experimental animal trials.Also, in a clinical trial, an experimental vaccine was observed to clear theamyloid plaques, however this did not have any significant effect on dementia(Homel.
, et al 2008). Similarly, PD is also a disease of protein misfolding,highlighted by the aggregation of a-synuclein protein in Lewy body inclusion inthe brain. Lewy bodies is a key area of the brain responsible for movement. Forreasons that are not completely clear this protein are altered and aggregateinto Lewy bodies, tangles and plaques.
A great deal of research suggests that thisprocess is very closely linked to neurodegeneration. Although, studies of humangenetics have demonstrated that mutation of (A53T,A30P, E46K) and multiplication of the ?-syn gene are very closely related tofamilial PD and overexpression of human A53T mutant a-syn can lead to severemovement disorders in mice, the molecular mechanism of a-syn toxicity are notvery clear. Li et al (2013) found that mitochondrial dysfunction was very closelylinked to PD and A53T ?-syn selectively inhibited mitochondrial mobility.However, the impact of impaired mitochondrial induced by a-syn onneurodegeneration is still incompletely understood. Therefore, Bido, Soria,fan, bezard and Tieu, (2017) investigate whether protecting mitochondrialfunctioning will be able to decrease a-syn induced neurotoxicity in a vivoapproach.Despite The recent advancements in AD andPD genetics the etiology of these diseases remains unclear. Environmentalfactors have gained importance and oxidative stress have been found to play acentral role in the pathogenesis of these neurodegenerative diseases. Oxidativestress occurs when three is an imbalance between the production of reactiveoxygen species(ROS) and a biological system’s ability to detoxify the reactiveintermediates or to repair the resulting damage.
(Cenini , 2016). Although, different studies have investigatedthe changes of markers of oxidative damage on late stage AD patients, early stagesof AD progressions are extremely important to determine the role that oxidativedamage plays on the pathogenesis of the disease. Therefore, A study of brainswhich investigated AD in different stages demonstrated increased levels of4-hydroxyhezenal (HHE) (a marker of lipid peroxidation involved in the earlystages of the disease (Bradley, Xiong-Fister, Markesbery , 2012). Inthis study the authors quantified the levels of extractable and protein-bound HHE in the hippocampus/parahippocampus gyrus, (HPG),superior and middle temporal gyri(SMTG), and the cerebellum of mild cognitive impairment,preclinical AD, late stage AD and a normal control group.
using gas chromatographymass spectrometry, the authors found a significance increase in the levels ofextractable HHE in HPG of PCAD and LAD participants in comparison to normalcontrol group. However, no difference was found in HPG of MCI participants incomparison to the control group. Similarly, significant levels of elevationwere observed in protein bound HEE in HPG of MCI, PCAD, and LAD participants incomparison to the control group. It was further examined whether treatment withHHE will aid the survival of primary cortical neurons