Neurodegenerative Disease Alzheimer’s Disease


showed a protective effect of this allele towards FTLD, but the data were not replicated. A recent meta-analysis comprising a total of 364 FTD patients and 2,671 controls demonstrated an increased susceptibility to FTD in APOE*2 carriers.90


Concerning the APOE*2 allele in the development of FTLD, heterogeneous data have been obtained in different populations. Bernardi et al.85


Daniela Galimberti is a PhD Researcher in Neurological Sciences in the Department of Neurological Sciences at the University of Milan. She is Chair of the Subcommittee on Behavioural and Cognitive Neurology and Dementia of the European Neurological Society. Her main interests include genetics and biomolecular aspects of neurodegenerative disorders (primarily Alzheimer’s disease and frontotemporal lobar degeneration).


Besides pathogenic mutations, several polymorphisms have been reported to date, both in MAPT and GRN. An association between PSP and a dinucleotide repeat polymorphism in the intron between MAPT exons 9 and 10 was described in 1997.91


The alleles at this locus carry


11–15 repeats. Subsequently, two common MAPT haplotypes, named H1 and H2, were identified.92


Homozygosity of the more common allele H1 predisposes to PSP and CBD, but not to AD or Pick disease.92,93


Regarding GRN, an association of an SNP located in the promoter with an increased risk of developing FTLD in patients who did not carry causal mutations has recently been demonstrated.94


Lastly, a known polymorphism in MCP-1 (A-2518G) has been shown to exert a protective effect towards the development of FTLD,95


n whereas


NOS3 G894T (Glu298Asp) and NOS1 C276T SNPs likely increase the risk of developing FTLD.96,97


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Elio Scarpini is a Professor of Neurology in the Department of Neurological Sciences at the University of Milan and Chair of the Alzheimer Centre at the Policlinico Hospital. He is a member of the Executive Committee of the European Neurological Society. His main interests include clinical and basic aspects of neurodegenerative disorders.


Chiara Fenoglio is a PhD Researcher in Neurological Sciences in the Department of Neurological Sciences at the University of Milan. Her main interests include genetics and biomolecular aspects of neurodegenerative and demyelinating disorders.


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EUROPEAN NEUROLOGICAL REVIEW


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