Method for determining the risk of developing a neurological disease

Abstract

Methods and kits are provided for determining whether a subject is at risk of developing a neurological disease such as Alzheimer's disease and multiple sclerosis. The methods and kits are based on the detection of one or more nucleic acid variants in the MBL gene of the subject.

1 .- 26 . (canceled) 
     
     
         27 . A kit for determining whether a subject is at risk of developing a neurological disease, comprising: (a) a means for detecting the presence or absence of one or more nucleic acid variants in the MBL genes of said subject, for measuring the concentration of one or more MBL protein variants in said subject and/or for measuring the MBL functional activity in said subject; and (b) a means for determining, from the nucleic acid variants, the protein variant concentration and/or the functional activity detected with the means of step (a), whether the subject is at risk of developing a neurological disease. 
     
     
         28 . The kit according to  claim 27 , comprising: (a) a means for detecting the presence or absence of one or more nucleic acid variants at nucleic acid positions +154 (C>T), +161 (G>A) and/or +170 (G>A) of the MBL2 genes of said subject; and (b) a means for determining, from the nucleic acid variants detected with the means of step (a), whether the subject is at risk of developing a neurological disease, whereby the absence of nucleotide T at position +154 (variant D), nucleotide A at position +161 (variant B) and nucleotide A at position +170 (variant C) of the MBL2 gene indicates that the subject is at risk of developing Alzheimer's disease. 
     
     
         29 . The kit according to  claim 28 , comprising: (a) a means for detecting the MBL haplotype of said subject; and (b) a means for determining, from the haplotypes detected with the means of step (a), whether the subject is at risk of developing a neurological disease, whereby the absence of the haplotypes HYPD, LYPB and LYQC indicates that the subject is at risk of developing Alzheimer's disease. 
     
     
         30 . The kit according to  claim 27 , comprising: (a) a means for detecting the presence or absence of one or more nucleic acid variants at position −221 (G>C) of the MBL2 genes of said subject; and (b) a means for determining, from the nucleic acid variants detected with the means of step (a), whether the subject is at risk of developing a neurological disease, whereby the presence of a nucleotide C at position −221 (variant X) of the MBL2 gene indicates that the subject is at risk of developing Alzheimer's disease. 
     
     
         31 . The kit according to  claim 30 , comprising: (a) a means for detecting the MBL haplotype of said subject; and (b) a means for determining, from the haplotypes detected with the means of step (a), whether the subject is at risk of developing a neurological disease, whereby the presence of the haplotype LXPA indicates that the subject is at risk of developing Alzheimer's disease. 
     
     
         32 . The kit according to  claim 27 , comprising: (a) a means for detecting the MBL haplotype of said subject; and (b) a means for determining, from the haplotypes detected with the means of step (a), whether the subject is at risk of developing a neurological disease, whereby the presence of the haplotype LYPA indicates that the subject is at risk of developing multiple sclerosis. 
     
     
         33 . The kit according to  claim 27 , comprising: (a) an antibody that specifically recognizes the MBL protein variant that is measured; and (b) a means for determining, from the MBL protein variant concentration measured with the means of step (a), whether the subject is at risk of developing a neurological disease. 
     
     
         34 . The kit according to  claim 33 , comprising: (a) an antibody that specifically recognizes the MBL2 protein variant with C at amino acid position 52 (variant D), D at amino acid position 54 (variant B) and/or E at amino acid position 57 (variant C); and (b) a means for determining, from the MBL protein variant concentration measured with the means of step (a), whether the subject is at risk of developing a neurological disease, whereby the absence of the MBL2 protein variant with C at amino acid position 52 (variant D), D at position 54 (variant B) and E at position 57 (variant C) indicates that the subject is at risk of developing Alzheimer's disease. 
     
     
         35 . The kit according to any of  claims 27  to  34 , further characterized in that the means for determining whether the subject is at risk of developing a neurological disease comprises a predisposition risk algorithm taking into account at least one of the following: the MBL nucleic acid variants or haplotypes, the MBL protein variant concentration and/or the MBL functional activity, to determine the risk for developing a neurological disease. 
     
     
         36 . A kit for determining whether a subject is at risk of developing a neurological disease, comprising: (a) a means for detecting the presence or absence of one or more nucleic acid variants in the MBL gene of said subject, for measuring the concentration of one or more MBL protein variants in said subject and/or for measuring the MBL functional activity in said subject; and (b) a means for detecting the ApoE genotype, the presenilin-1 genotype, the presenilin-2 genotype, a mutation in the APP gene and/or a CYP46 polymorphism in said subject.