**2. Clinical understanding and differential diagnosis among neurodegenerative diseases**

Neurodegenerative diseases encompass different pathologies with the common feature of progressive loss of structure or function of neurons.

Over the last years, evidence evolved of common pathological processes in different neurodegenerative diseases like accumulation of neurofilaments, protein degradation and induced cell death. For example, accumulated TDP-43 is found in sporadic ALS cases, which links this disease to fronto-temporal dementias (FTD) (Neumann et al., 2006). Furthermore, on behavioural level there is accumulating evidence for a common cognitive decline in some ALS patients and in patients with FTD.

Genetics provide further evidence for an association between different neurodegenerative diseases like polyglutamine repeats in Huntington's disease and spinocerebellar ataxias and mutations in the alpha-synuclein in Parkinson's Disease, dementia with Lewy bodies and multiple system atrophy. Furthermore, mitochondrial dysfunction, disturbed axonal transport and endothelial dysfunction are common pathological hallmarks found in different neurodegenerative diseases. In clinical routine, differential diagnosis is usually done on clinical basis. According to clinical criteria, Amyotrophic lateral sclerosis is regarded as a disease of the peripheral and central nervous system and the other most common neurodegenerative diseases like dementias, Parkinson's disease and Huntington's disease are primarily regarded as diseases of the central nervous system (Hacke, 2007). However, evidence for overlaps in molecular or cellular pathways question this classification and suggests a major overlap of different neurodegenerative pathologies in central and peripheral nervous system (Braak et al., 2006b; Braak & Del Tredici, 2011a, 2011b; Grammas et al., 2011; Neumann et al., 2006). New imaging techniques carry the hope of revolutionizing the diagnosis of neurodegenerative disease to improve staging of patients and follow disease progression and treatment trial efficacy.
