The therapeutic importance of understanding mechanisms of neuronal cell death in neurodegenerative disease

Table 1 Examples of the Relationship Between Lesions, Proteins and Causal Genes in Neurodegenerative Diseases

Disease	Lesions	Major Protein In Deposit	Genetic Alterations
Alzheimer's	Plaques NFT	Aβ tau	Mutations/Multiplication in APP and Presenilin genes cause altered Aβ production
Parkinson's (classic)¹	Lewy Body	α-synuclein	Mutation/Multiplication of α-synuclein gene
FTDP-17tau	NFT	tau	Mutations in tau
FTLDu	Ubiquitin positive inclusions	TDP-43	Mutations in Granulin gene, evidence that Granulin interacts with TDP-43
Polyglutamine Diseases (e.g. Huntington's, SCA)	Inclusions of expanded Poly Q protein	PolyQ encoding protein	Expanded CAG repeats encoded stretches of Poly Q
ALS	Ubiquitin positive inclusions	TDP-43	Mutations in TDP-43
ALS	Ubiquitin positive inclusions	Inclusions are TDP negative	Mutations in SOD1

¹ Numerous genes have now been implicated in Parkinsonism, some of these genes result in classic Lewy body pathology others do not, and some such as LRRK2 can produce distinct pathologies even within a single family.

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