We concluded that DBP-exposure resulted only in sporadic germ cell aggregation in xenografted human testes, but when aggregation was induced, it affected differentiated [MAGE-A4 positive (MAGE-A4pos)] germ cells, as in rats.
This is also important because while most familial forms of AD might result from mutations that affect the rate of Aβ synthesis and aggregation, sporadic AD might be the result of alterations in Aβ clearance (Fig. 7).
While in rare familial cases mutations in α-syn might contribute to oligomerization [11], it is unclear what triggers α-syn aggregation in sporadic forms of LBD.
Discovery of these genes have strongly implicated certain cellular processes in the etiology of both inherited and sporadic disease; namely protein aggregation and impairment of the ubiquitin proteasome system, mitochondrial dysfunction, oxidative stress and protein phosphorylation [8].
The molecular incident responsible for triggering tau aggregation in sporadic tauopathies is unknown.
Interestingly, both genetic mutations (familiar) or environmental insults (sporadic) can trigger protein aggregation diseases, implying that a common mechanism may exist to link these clinically distinct diseases.
Mutations of the human desmin gene on chromosome 2q35 cause autosomal dominant, autosomal recessive and sporadic forms of protein aggregation myopathies and cardiomyopathies.
Hence, dendritic tau hyperphosphorylation and aggregation in sporadic Alzheimer's disease may be a secondary or even compensatory phenomenon due to slowly progressing deafferentation/disconnection in the aging brain rather than the cause of dendritic spine loss or synaptic failure.
Although several monogenic forms of cerebral small vessel disease with early onset have been described, the majority of patients with subcortical VaD represents sporadic cases with enhanced aggregation in families but without a clear Mendelian pattern of inheritance.
The potential of wild type Tau to undergo prion-like Tau seeding allows a (cautious) extrapolation of our data in the context of AD or sporadic Tauopathies, characterized by aggregation of wild type Tau.
