AD

PD

Dementia

·         Mutations of the β-amyloid (Aβ) precursor protein on chromosome 21, cause Alzheimer disease (AD) [18].

·         Lewy bodies are a marker protein aggregation in PD, are also frequently observed in cases of classic AD, including in patients with mutations in APP, PSEN1, and PSEN2 [19,20].

·         The main neuropathologic hallmark of PD is the accumulation of α-synuclein in neurons in the form of Lewy bodies [21].

·         Lewy Body Dementia (LBD) is a common type of degenerative Dementia in elderly people [22].

·         Many patients with LBD have AD pathology because they have Lewy bodies, cortical amyloid plaques and neurofibrillary tangles in common [22].

In transgenic mice, the accumulation of α-synuclein could significantly disrupt cognition [20].

It is generally believed that oxidative stress and mitochondrial dysfunction are likely to be the common mechanisms in PD, AD and Dementia [23].

·         Linkage analysis showed that the better part of AD signal on chromosome 12q13 near 50 Mb was actually caused by a subset of families fulfilling neuropathological criteria for LBD (i.e., 8 of 54 families) [24-26].

·         Mutations in microtubule-associated protein tau.

·         Abundance of 4-repeat tau has also been frequently associated with PD. This possibly suggests a common tau-related pathogenic mechanism shared by FTD and late-onset PD [27].

·         Fully penetrant autosomal dominant mutations in 3 genes (i.e. APP, PSEN1, and PSEN2) has been shown to cause AD [28-30].

·         Mutations in at least 5 genes has been shown to cause familial early-onset Parkinsonisms:

--(α-synuclein [SNCA or PARK1] [31];

--parkin [PRKN or PARK2] [32]

--DJ-1 [DJ1 or PARK7] [33]

--PTEN-induced putative kinase I [PINK1 or PARK6] [34];

--leucine-rich repeat kinase2 [LRRK2 or PARK8] [35,36].

·         Rare missense mutations

In MAPT leads to a syndrome of fronto-temporal dementia (FTD) with parkinsonism linked to chromosome 17 [FTDP-17] [24].