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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.