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Table 1 Detection of spirochetes in Alzheimer disease

From: Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria

Authors N Mat Meth AD CTRL Cult Serol
Detection of all types of spirochetes
Miklossy, 1993 & Miklossy et al., 1994 [70, 80] 27 Brain, Bl, CSF DF, HC, IHC, EM, AFM 14/14 0/13** 14/14 (Bl 4/5) Nd
Miklossy, 1994 [81] 12
5
Brain
Bl
DF
DF
8/8
5/5
0/4** 8/8
Nd
Nd
Nd
Miklossy et al., 1995 [82] 24
10***
Brain DNA-DAPI 20/20
10/10***
0/4** Nd Nd
Miklossy et al., 1996, Miklossy, 1998 [83, 84] 54 Brain IHC 32/32
12/12*
0/10** Nd
Nd
Nd
Nd
McLaughlin et al., 1999 [90] 7
28
Brain
Bl
DF, EM 0/7
1/22
0/6 Nd
Nd
Nd
Nd
Total: Various types of spirochetes detected using neutral techniques
Brain: AD N = 102, AD 64/71, CTRL 0/31", P = 4.8 × 10 -18 , OR" = 274, 95% CI = 32-11345
Brain: AD, mild AD N = 114, AD 76/83, CTRL 0/31", P = 1 × 10 -19 , OR" = 325, 95% CI = 38-13440
Brain, Bl, CSF: AD, mild AD N = 147, AD 82/110, CTRL 0/37", P = 1.1 × 10 -15 , OR" = 105, 95% CI = 13-4329
Periodontal pathogen spirochetes
Riviere et al, 2002 [96] 34 Brain, PCR, IHC 15/16 6/18 Nd Nd
Total: Periodontal pathogen spirochetes detected in the brain
Brain: AD, N = 34, AD 15/16, CTRL 6/18, P = 3.6 × 10 -4 , OR = 30, 95%CI = 2.8-1364
Borrelia burgdorferi
MacDonald & Miranda1987 [98] 2 Brain IHC 1/1 0/1 + Nd
MacDonald, 1988 [99] 1 Brain DF, IHC 1/1   + Nd
Pappolla et al., 1989 [103] 10 Brain EM, IHC, Wbl 0/6 0/4 - Nd
Miklossy, 1993 and Miklossy et al., 2004 [70, 85] 27*** Brain Bl, CSF Cult, IHC, EM, ISH, 16SrRNA 3/14*** 0/13*** 3/14 2/14
Miklossy, 1993 [70] 1 Brain IHC 1/1   Nd 1/1
Gutacker et al., 1998 [104] 10 Brain PCR 0/10   - Nd
Marques et al., 2000 [105] 30 Brain PCR 0/15 0/15 Nd Nd
Riviere et al., 2002 [96] 34*** Brain PCR, seq 5/16*** 1/18*** Nd Nd
Meer-Scherrer et al., 2006 [100] 1 Brain PCR 1/1   Nd 1/1
MacDonald, 2006 [101, 102] 11 Brain PCR, IHC 7/10 0/1 Nd 1/1
Total: All studies detecting Borrelia burgdorferi
Brain: AD N = 127, AD 19/75, CTRL 1/52, P = 2.9 × 10 -4 , OR = 17, 95%CI = 2-732
  1. Total: All studies detecting spirochetes
  2. Brain: AD N = 202, AD 90/131, CTRL 6/71, P = 1.7 × 10 -17 , OR = 23, 95%CI = 9-71
  3. Brain: AD, mild AD N = 214, AD 102/143, CTRL 6/71, P = 1.5 × 10 -19 , OR = 26, 95% CI = 10-80
  4. Brain, Bl, CSF: AD, mild AD N = 247, AD 108/170, CTRL 6/77, P = 1.5 × 10 -17 , OR = 20, 95% CI = 8-60
  5. Data reviewed in the literature with respect to the detection of all types of spirochetes using neutral techniques and the specific detection of periodontal pathogen Treponemas and Borrelia burgdorferi. Results of the statistical analysis are given for each group and for all studies together. N = total number of cases investigated, AD = Alzheimer disease, CTRL = control, Mat = material, Meth = methods, Cult = culture, Serol = serology, AD = Number of AD cases positive for spirochetes/number of AD cases analyzed, CTRL = Number of control cases positive for spirochetes/number of control cases analyzed, Bl = blood, CSF = cerebrospinal fluid, EM = electron microscopy, AFM = atomic force microscopy, DF = dark field microscopy, HC = histochemistry (Warthin and Starry, Bosma-Steiner silver stain for spirochetes), IHC = immunohistochemistry, ISH = in situ hybridization, PCR = polymerase chain reaction, Bb = Borrelia burgdorferi, Wbl = Western blot, P = exact value of the significance calculated by the Fischer test, OR = Odds Ratio, CI = 95% confidence interval, + = positive, - = negative, Nd = not done, seq = sequence analysis, * = cases with mild or moderate AD-type cortical changes, ** = controls without any AD-type changes, *** = cases from previous studies, which were subtracted when the total number of cases of studies were considered, " = the number of 0 positive control was changed to 1 in order to calculate the exact OR and CI values.