Method for diagnosing amyotrophic lateral sclerosis using signal peptide as indicator

1. A method for aiding detection of amyotrophic lateral sclerosis (ALS), the method comprising:

analyzing to determine a presence or an absence of an ALS-associated signal peptide in a bodily fluid from a test subject or analyzing to determine a degree of abundance of the ALS-associated signal peptide when present, and

comparing the presence or the absence of the ALS-associated signal peptide or the degree of abundance of the ALS-associated signal peptide in the bodily fluid from the test subject with a reference level that has been set based on results obtained by having determined the presence or the absence of the ALS-associated signal peptide, or by having determined the degree of abundance of the ALS-associated signal peptide in a bodily fluid from at least one healthy subject, wherein

a molecular weight of the ALS-associated signal peptide is:

1405.71±2, 1406.49±2, 1409.40±2, 1410.97±2, 1418.70±2, 1426.68±2, 1437.62±2, 1445.77±2, 1451.61±2, 1456.44±2, 1458.88±2, 1466.24±2, 1468.86±2, 1472.12±2, 1476.87±2, 1482.60±2, 1493.58±2, 1495.42±2, 1496.52±2, 1497.16±2, 1498.88±2, 1502.40±2, 1505.52±2, 1508.76±2, 1510.50±2, 1516.64±2, 1521.93±2, 1529.32±2, 1530.37±2, 1533.52±2, 1539.36±2, 1544.22±2, 1553.72±2, 1555.72±2, 1560.24±2, 1566.20±2, 1567.20±2, 1567.74±2, 1575.70±2, 1578.07±2, 1580.91±2, 1589.58±2, 1592.55±2, 1597.25±2, 1608.53±2, 1609.36±2, 1610.62±2, 1616.12±2, 1629.15±2, 1639.39±2, 1640.36±2, 1646.58±2, 1655.72±2, 1657.97±2, 1659.24±2, 1660.46±2, 1662.16±2, 1679.09±2, 1682.54±2, 1683.12±2, 1687.34±2, 1688.14±2, 1691.08±2, 1691.75±2, 1694.76±2, 1695.74±2, 1700.65±2, 1702.19±2, 1705.53±2, 1708.77±2, 1712.10±2, 1714.63±2, 1715.56±2, 1719.51±2, 1721.61±2, 1726.31±2, 1737.85±2, 1739.71±2, 1743.69±2, 1761.79±2, 1769.93±2, 1774.13±2, 1775.70±2, 1786.39±2, 1788.03±2, 1790.80±2, 1796.23±2, 1797.49±2, 1800.34±2, 1801.79±2, 1804.45±2, 1810.72±2, 1812.31±2, 1813.77±2, 1817.26±2, 1818.66±2, 1819.34±2, 1819.93±2, 1821.71±2, 1822.73±2, 1829.48±2, 1831.81±2, 1832.41±2, 1836.18±2, 1837.33±2, 1840.84±2, 1849.81±2, 1854.68±2, 1858.34±2, 1864.19±2, 1866.06±2, 1875.28±2, 1876.50±2, 1878.25±2, 1890.21±2, 1891.32±2, 1893.00±2, 1904.69±2, 1911.46±2, 1913.68±2, 1916.02±2, 1919.35±2, 1927.13±2, 1931.84±2, 1934.86±2, 1935.52±2, 1936.83±2, 1937.87±2, 1941.22±2, 1944.97±2, 1948.39±2, 1952.47±2, 1957.80±2, 1962.82±2, 1969.82±2, 1972.54±2, 1975.58±2, 1976.51±2, 1977.70±2, 1979.29±2, 1988.46±2, 1991.91±2, 1995.37±2, 2009.91±2, 2011.18±2, 2013.86±2, 2023.97±2, 2027.73±2, 2030.95±2, 2032.69±2, 2039.29±2, 2043.12±2, 2045.68±2, 2051.76±2, 2055.50±2, 2059.05±2, 2062.98±2, 2065.57±2, 2066.09±2, 2074.03±2, 2075.32±2, 2079.80±2, 2083.74±2, 2084.36±2, 2085.85±2, 2089.53±2, 2092.25±2, 2092.80±2, 2097.03±2, 2099.42±2, 2111.39±2, 2113.10±2, 2115.77±2, 2120.37±2, 2126.55±2, 2137.63±2, 2139.15±2, 2140.48±2, 2143.42±2, 2146.46±2, 2149.85±2, 2151.02±2, 2160.22±2, 2161.68±2, 2167.09±2, 2167.78±2, 2168.75±2, 2173.75±2, 2177.51±2, 2179.25±2, 2184.93±2, 2185.65±2, 2186.28±2, 2190.18±2, 2191.02±2, 2192.84±2, 2196.47±2, 2199.82±2, 2201.22±2, 2204.02±2, 2207.10±2, 2211.58±2, 2216.77±2, 2218.45±2, 2219.30±2, 2220.56±2, 2222.74±2, 2226.96±2, 2228.22±2, 2231.60±2, 2239.71±2, 2244.01±2, 2251.78±2, 2254.83±2, 2256.53±2, 2261.91±2, 2266.45±2, 2268.58±2, 2274.97±2, 2276.04±2, 2278.67±2, 2281.09±2, 2285.01±2, 2289.43±2, 2290.85±2, 2292.35±2, 2295.92±2, 2296.92±2, 2301.71±2, 2302.50±2, 2303.21±2, 2305.43±2, 2307.22±2, 2314.24±2, 2314.81±2, 2317.68±2, 2325.30±2, 2327.73±2, 2341.14±2, 2342.87±2, 2344.45±2, 2351.97±2, 2353.99±2, 2355.29±2, 2357.54±2, 2367.75±2, 2375.59±2, 2378.35±2, 2380.39±2, 2393.64±2, 2402.11±2, 2404.01±2, 2406.49±2, 2412.79±2, 2414.25±2, 2415.20±2, 2416.30±2, 2431.13±2, 2434.36±2, 2438.19±2, 2439.22±2, 2444.37±2, 2451.90±2, 2453.96±2, 2455.44±2, 2456.62±2, 2459.43±2, 2462.31±2, 2464.16±2, 2470.97±2, 2478.17±2, 2479.28±2, 2484.18±2, 2500.40±2, 2502.64±2, 2504.73±2, 2507.42±2, 2509.21±2, 2515.26±2, 2517.43±2, 2519.07±2, 2527.31±2, 2531.06±2, 2532.26±2, 2546.08±2, 2554.96±2, 2559.48±2, 2564.01±2, 2571.26±2, 2578.45±2, 2581.25±2, 2583.37±2, 2584.81±2, 2587.01±2, 2588.90±2, 2593.68±2, 2596.11±2, 2603.33±2, 2608.20±2, 2613.31±2, 2614.91±2, 2622.46±2, 2629.26±2, 2633.69±2, 2634.61±2, 2640.51±2, 2641.73±2, 2652.85±2, 2655.08±2, 2665.15±2, 2670.00±2, 2682.80±2, 2696.41±2, 2697.73±2, 2698.27±2, 2699.82±2, 3302.01±2, 3303.21±2, 3309.84±2, 3323.89±2, 3330.34±2, 3337.92±2, 3366.84±2, 3370.39±2, 3378.18±2, 3380.43±2 or 3384.77±2, wherein the degree of abundance of any of the ALS-associated signal peptides having the following molecular weights out of the tested ALS-associated signal peptides in the bodily fluid from the test subject is confirmed to be high in comparison with the reference level:

1405.71±2, 1406.49±2, 1409.40±2, 1410.97±2, 1418.70±2, 1426.68±2, 1437.62±2, 1445.77±2, 1451.61±2, 1456.44±2, 1458.88±2, 1466.24±2, 1468.86±2, 1472.12±2, 1476.87±2, 1482.60±2, 1493.58±2, 1495.42±2, 1496.52±2, 1498.88±2, 1502.40±2, 1505.52±2, 1508.76±2, 1510.50±2, 1516.64±2, 1521.93±2, 1529.32±2, 1530.37±2, 1533.52±2, 1539.36±2, 1544.22±2, 1553.72±2, 1555.72±2, 1560.24±2, 1566.20±2, 1567.20±2, 1575.70±2, 1578.07±2, 1580.91±2, 1589.58±2, 1592.55±2, 1597.25±2, 1608.53±2, 1609.36±2, 1610.62±2, 1616.12±2, 1629.15±2, 1639.39±2, 1640.36±2, 1646.58±2, 1655.72±2, 1657.97±2, 1659.24±2, 1660.46±2, 1662.16±2, 1679.09±2, 1682.54±2, 1683.12±2, 1687.34±2, 1688.14±2, 1691.08±2, 1691.75±2, 1694.76±2, 1695.74±2, 1700.65±2, 1702.19±2, 1708.77±2, 1712.10±2, 1714.63±2, 1715.56±2, 1719.51±2, 1721.61±2, 1726.31±2, 1737.85±2, 1739.71±2, 1743.69±2, 1761.79±2, 1769.93±2, 1774.13±2, 1775.70±2, 1786.39±2, 1788.03±2, 1790.80±2, 1796.23±2, 1797.49±2, 1800.34±2, 1801.79±2, 1804.45±2, 1810.72±2, 1812.3±21, 1813.77±2, 1817.26±2, 1818.66±2, 1819.93±2, 1821.71±2, 1822.73±2, 1829.48±2, 1832.41±2, 1836.18±2, 1837.33±2, 1840.84±2, 1849.81±2, 1854.68±2, 1858.34±2, 1864.19±2, 1866.06±2, 1875.28±2, 1876.50±2, 1878.25±2, 1890.21±2, 1891.32±2, 1893.00±2, 1904.69±2, 1911.46±2, 1913.68±2, 1916.02±2, 1919.35±2, 1927.13±2, 1931.84±2, 1934.86±2, 1936.83±2, 1937.87±2, 1941.22±2, 1944.97±2, 1948.39±2, 1952.47±2, 1957.80±2, 1962.82±2, 1969.82±2, 1972.54±2, 1975.58±2, 1976.51±2, 1977.70±2, 1979.29±2, 1988.46±2, 1991.91±2, 1995.37±2, 2009.91±2, 2011.18±2, 2013.86±2, 2023.97±2, 2027.73±2, 2030.95±2, 2032.69±2, 2039.29±2, 2043.12±2, 2045.68±2, 2051.76±2, 2059.05±2, 2062.98±2, 2066.09±2, 2074.03±2, 2075.32±2, 2079.80±2, 2083.74±2, 2085.85±2, 2089.53±2, 2092.80±2, 2097.03±2, 2099.42±2, 2111.39±2, 2113.10±2, 2115.77±2, 2120.37±2, 2126.55±2, 2137.63±2, 2139.15±2, 2143.42±2, 2146.46±2, 2149.85±2, 2151.02±2, 2160.22±2, 2161.68±2, 2167.09±2, 2168.75±2, 2173.75±2, 2177.51±2, 2179.25±2, 2185.65±2, 2186.28±2, 2190.18±2, 2191.02±2, 2192.84±2, 2196.47±2, 2199.82±2, 2201.22±2, 2204.02±2, 2207.10±2, 2211.58±2, 2216.77±2, 2218.45±2, 2219.30±2, 2220.56±2, 2222.74±2, 2226.96±2, 2228.22±2, 2231.60±2, 2239.71±2, 2244.01±2, 2251.78±2, 2254.83±2, 2256.53±2, 2261.91±2, 2266.45±2, 2268.58±2, 2274.97±2, 2276.04±2, 2278.67±2, 2281.09±2, 2285.01±2, 2289.43±2, 2290.85±2, 2292.35±2, 2295.92±2, 2296.92±2, 2301.71±2, 2302.50±2, 2303.21±2, 2305.43±2, 2307.22±2, 2314.24±2, 2317.68±2, 2325.30±2, 2341.14±2, 2342.87±2, 2344.45±2, 2351.97±2, 2353.99±2, 2355.29±2, 2357.54±2, 2367.75±2, 2375.59±2, 2378.35±2, 2380.39±2, 2393.64±2, 2402.11±2, 2404.01±2, 2406.49±2, 2412.79±2, 2414.25±2, 2415.20±2, 2416.30±2, 2431.13±2, 2434.36±2, 2438.19±2, 2439.22±2, 2444.37±2, 2451.90±2, 2453.96±2, 2455.44±2, 2456.62±2, 2459.43±2, 2462.31±2, 2464.16±2, 2470.97±2, 2478.17±2, 2479.28±2, 2484.18±2, 2500.40±2, 2502.64±2, 2504.73±2, 2507.42±2, 2509.21±2, 2515.26±2, 2517.43±2, 2519.07±2, 2527.31±2, 2531.06±2, 2532.26±2, 2546.08±2, 2554.96±2, 2559.48±2, 2564.01±2, 2571.26±2, 2578.45±2, 2581.25±2, 2583.37±2, 2584.81±2, 2587.01±2, 2588.90±2, 2593.68±2, 2596.11±2, 2603.33±2, 2608.20±2, 2613.31±2, 2614.91±2, 2622.46±2, 2629.26±2, 2633.69±2, 2634.61±2, 2640.51±2, 2641.73±2, 2652.85±2, 2655.08±2, 2665.15±2, 2670.00±2, 2682.80±2, 2696.41±2, 2698.27±2, 2699.82±2, 3302.01±2, 3303.21±2, 3323.89±2, 3330.34±2, 33317.92±2, 3366.84±2, 3370.39±2, 3378.18±2, 3380.43±2 and 3384.77±2, wherein

the presence or the absence or the degree of abundance of the ALS-associated signal peptide in the bodily fluid from the test subject is tested with a mass spectrometer, wherein

further comprising:

immobilizing the bodily fluid on a thermoplastic resin before the presence or the absence and the degree of abundance of the ALS-associated signal peptide in the bodily fluid is tested, and wherein

the presence or the absence and the degree of abundance of the ALS-associated signal peptide in the bodily fluid immobilized on the thermoplastic resin is determined by matrix assisted laser desorption/ionization-time of flight mass spectrometry.

2. The method according to claim 1 , wherein an amino acid sequence of the ALS-associated signal peptide is any of amino acid sequences represented by SEQ ID Nos: 1 to 16, 21 to 27, 29 to 46, 53 to 67, 72 to 87, 94 to 108, 118 to 172, 179 to 243, 248 to 295, 297 to 304, 307 to 317, 320 to 333, 337 to 354, 359 to 422, 424, 425, 430 to 585, 587 to 593, 595 to 605, 607 to 693, 696, 699 to 777, 786 to 902, 906 to 914, 918 to 945, 947 to 983, 990 to 1029, 1042 to 1201, 1208 to 1217, 1230 to 1566, 1569 to 1571 and 1574 to 1580.

3. The method according to claim 1 , wherein at least the degree of abundance of an ALS-associated signal peptide with a molecular weight of 1502.40±2, 1521.93±2, 1629.15±2, 1682.54±2, 1691.75±2, 1705.53±2, 1821.71±2, 1836.18±2, 1948.39±2, 2011.18±2, 2092.80±2, 2099.42±2, 2177.51±2, 2179.25±2, 2186.28±2, 2211.58±2, 2226.96±2, 2254.83±2, 2278.67±2, 2290.85±2, 2292.35±2, 2502.64±2, 2640.51±2, 2698.27±2 or 3330.34±2 is tested.

4. The method according to claim 3 , wherein an amino acid sequence constituting the ALS-associated signal peptide is any of amino acid sequences represented by SEQ ID Nos: 1 to 180.

5. The method according to claim 1 , wherein at least 10 kinds of ALS-associated signal peptides having molecular weights differing by at least 3 from each other are tested in the bodily fluid from the test subject.

6. The method according to claim 1 , wherein the bodily fluid is a cerebrospinal fluid.

7. A method for aiding detection of amyotrophic lateral sclerosis (ALS), the method comprising:

analyzing to determine a presence or an absence of an ALS-associated signal peptide in a bodily fluid from a test subject or analyzing to determine a degree of abundance of the ALS-associated signal peptide when present, and

comparing the presence or the absence of the ALS-associated signal peptide or the degree of abundance of the ALS-associated signal peptide in the bodily fluid from the test subject with a reference level that has been set based on results obtained by having determined the presence or the absence of the ALS-associated signal peptide, or by having determined the degree of abundance of the ALS-associated signal peptide in a bodily fluid from at least one healthy subject, wherein

a molecular weight of the ALS-associated signal peptide is:

1405.71±2, 1406.49±2, 1409.40±2, 1410.97±2, 1418.70±2, 1426.68±2, 1437.62±2, 1445.77±2, 1451.61±2, 1456.44±2, 1458.88±2, 1466.24±2, 1468.86±2, 1472.12±2, 1476.87±2, 1482.60±2, 1493.58±2, 1495.42±2, 1496.52±2, 1497.16±2, 1498.88±2, 1502.40±2, 1505.52±2, 1508.76±2, 1510.50±2, 1516.64±2, 1521.93±2, 1529.32±2, 1530.37±2, 1533.52±2, 1539.36±2, 1544.22±2, 1553.72±2, 1555.72±2, 1560.24±2, 1566.20±2, 1567.20±2, 1567.74±2, 1575.70±2, 1578.07±2, 1580.91±2, 1589.58±2, 1592.55±2, 1597.25±2, 1608.53±2, 1609.36±2, 1610.62±2, 1616.12±2, 1629.15±2, 1639.39±2, 1640.36±2, 1646.58±2, 1655.72±2, 1657.97±2, 1659.24±2, 1660.46±2, 1662.16±2, 1679.09±2, 1682.54±2, 1683.12±2, 1687.34±2, 1688.14±2, 1691.08±2, 1691.75±2, 1694.76±2, 1695.74±2, 1700.65±2, 1702.19±2, 1705.53±2, 1708.77±2, 1712.10±2, 1714.63±2, 1715.56±2, 1719.51±2, 1721.61±2, 1726.31±2, 1737.85±2, 1739.71±2, 1743.69±2, 1761.79±2, 1769.93±2, 1774.13±2, 1775.70±2, 1786.39±2, 1788.03±2, 1790.80±2, 1796.23±2, 1797.49±2, 1800.34±2, 1801.79±2, 1804.45±2, 1810.72±2, 1812.31±2, 1813.77±2, 1817.26±2, 1818.66±2, 1819.34±2, 1819.93±2, 1821.71±2, 1822.73±2, 1829.48±2, 1831.81±2, 1832.41±2, 1836.18±2, 1837.33±2, 1840.84±2, 1849.81±2, 1854.68±2, 1858.34±2, 1864.19±2, 1866.06±2, 1875.28±2, 1876.50±2, 1878.25±2, 1890.21±2, 1891.32±2, 1893.00±2, 1904.69±2, 1911.46±2, 1913.68±2, 1916.02±2, 1919.35±2, 1927.13±2, 1931.84±2, 1934.86±2, 1935.52±2, 1936.83±2, 1937.87±2, 1941.22±2, 1944.97±2, 1948.39±2, 1952.47±2, 1957.80±2, 1962.82±2, 1969.82±2, 1972.54±2, 1975.58±2, 1976.51±2, 1977.70±2, 1979.29±2, 1988.46±2, 1991.91±2, 1995.37±2, 2009.91±2, 2011.18±2, 2013.86±2, 2023.97±2, 2027.73±2, 2030.95±2, 2032.69±2, 2039.29±2, 2043.12±2, 2045.68±2, 2051.76±2, 2055.50±2, 2059.05±2, 2062.98±2, 2065.57±2, 2066.09±2, 2074.03±2, 2075.32±2, 2079.80±2, 2083.74±2, 2084.36±2, 2085.85±2, 2089.53±2, 2092.25±2, 2092.80±2, 2097.03±2, 2099.42±2, 2111.39±2, 2113.10±2, 2115.77±2, 2120.37±2, 2126.55±2, 2137.63±2, 2139.15±2, 2140.48±2, 2143.42±2, 2146.46±2, 2149.85±2, 2151.02±2, 2160.22±2, 2161.68±2, 2167.09±2, 2167.78±2, 2168.75±2, 2173.75±2, 2177.51±2, 2179.25±2, 2184.93±2, 2185.65±2, 2186.28±2, 2190.18±2, 2191.02±2, 2192.84±2, 2196.47±2, 2199.82±2, 2201.22±2, 2204.02±2, 2207.10±2, 2211.58±2, 2216.77±2, 2218.45±2, 2219.30±2, 2220.56±2, 2222.74±2, 2226.96±2, 2228.22±2, 2231.60±2, 2239.71±2, 2244.01±2, 2251.78±2, 2254.83±2, 2256.53±2, 2261.91±2, 2266.45±2, 2268.58±2, 2274.97±2, 2276.04±2, 2278.67±2, 2281.09±2, 2285.01±2, 2289.43±2, 2290.85±2, 2292.35±2, 2295.92±2, 2296.92±2, 2301.71±2, 2302.50±2, 2303.21±2, 2305.43±2, 2307.22±2, 2314.24±2, 2314.81±2, 2317.68±2, 2325.30±2, 2327.73±2, 2341.14±2, 2342.87±2, 2344.45±2, 2351.97±2, 2353.99±2, 2355.29±2, 2357.54±2, 2367.75±2, 2375.59±2, 2378.35±2, 2380.39±2, 2393.64±2, 2402.11±2, 2404.01±2, 2406.49±2, 2412.79±2, 2414.25±2, 2415.20±2, 2416.30±2, 2431.13±2, 2434.36±2, 2438.19±2, 2439.22±2, 2444.37±2, 2451.90±2, 2453.96±2, 2455.44±2, 2456.62±2, 2459.43±2, 2462.31±2, 2464.16±2, 2470.97±2, 2478.17±2, 2479.28±2, 2484.18±2, 2500.40±2, 2502.64±2, 2504.73±2, 2507.42±2, 2509.21±2, 2515.26±2, 2517.43±2, 2519.07±2, 2527.31±2, 2531.06±2, 2532.26±2, 2546.08±2, 2554.96±2, 2559.48±2, 2564.01±2, 2571.26±2, 2578.45±2, 2581.25±2, 2583.37±2, 2584.81±2, 2587.01±2, 2588.90±2, 2593.68±2, 2596.11±2, 2603.33±2, 2608.20±2, 2613.31±2, 2614.91±2, 2622.46±2, 2629.26±2, 2633.69±2, 2634.61±2, 2640.51±2, 2641.73±2, 2652.85±2, 2655.08±2, 2665.15±2, 2670.00±2, 2682.80±2, 2696.41±2, 2697.73±2, 2698.27±2, 2699.82±2, 3302.01±2, 3303.21±2, 3309.84±2, 3323.89±2, 3330.34±2, 3337.92±2, 3366.84±2, 3370.39±2, 3378.18±2, 3380.43±2 or 3384.77±2, wherein

further comprising:

confirming that the degree of abundance of any of the ALS-associated signal peptides having the following molecular weights out of the tested ALS-associated signal peptides in the bodily fluid from the test subject is low in comparison with the reference level:

1497.16±2, 1567.74±2, 1705.53±2, 1819.34±2, 1831.81±2, 1935.52±2, 2055.50±2, 2065.57±2, 2084.36±2, 2092.25±2, 2140.48±2, 2167.78±2, 2184.93±2, 2314.81±2, 2327.73±2, 2697.73±2 and 3309.84±2, wherein

the presence or the absence or the degree of abundance of the ALS-associated signal peptide in the bodily fluid from the test subject is tested with a mass spectrometer, wherein

further comprising:

immobilizing the bodily fluid on a thermoplastic resin before the presence or the absence and the degree of abundance of the ALS-associated signal peptide in the bodily fluid is tested, and wherein

the presence or the absence and the degree of abundance of the ALS-associated signal peptide in the bodily fluid immobilized on the thermoplastic resin is determined by matrix assisted laser desorption/ionization-time of flight mass spectrometry.

8. The method according to claim 7 , wherein an amino acid sequence of the ALS-associated signal peptide is any of amino acid sequences represented by SEQ ID Nos: 68, 69, 296, 357, 429, 903 to 905, 1223 to 1229, 1572 and 1573.

9. The method according to claim 7 , wherein at least the degree of abundance of an ALS-associated signal peptide with a molecular weight of 1502.40±2, 1521.93±2, 1629.15±2, 1682.54±2, 1691.75±2, 1705.53±2, 1821.71±2, 1836.18±2, 1948.39±2, 2011.18±2, 2092.80±2, 2099.42±2, 2177.51±2, 2179.25±2, 2186.28±2, 2211.58±2, 2226.96±2, 2254.83±2, 2278.67±2, 2290.85±2, 2292.35±2, 2502.64±2, 2640.51±2, 2698.27±2 or 3330.34±2 is tested.

10. The method according to claim 9 , wherein an amino acid sequence constituting the ALS-associated signal peptide is any of amino acid sequences represented by SEQ ID Nos: 1 to 180.

11. The method according to claim 7 , wherein at least 10 kinds of ALS-associated signal peptides having molecular weights differing by at least 3 from each other are tested in the bodily fluid from the test subject.

12. The method according to claim 7 , wherein the bodily fluid is a cerebrospinal fluid.