Alzheimer's Disease: APP, Gamma Secretase, APOE, CLU, CR1, PICALM, ABCA7, BIN1, CD2AP, CD33, EPHA1, and MS4A2, and Their Relationships with Herpes Simplex, C. Pneumoniae, Other Suspect Pathogens, and the Immune System

Table 1

Viral, bacterial, and fungal protein homology with beta-amyloid (top), NGF (middle), or tau (bottom); Predicted B cell epitope segments were compared with Borrelia burgdorferi, C. neoformans, C. pneumoniae, H. pylori, P. gingivalis and herpes viruses (HSV1, HHV6, and cytomegalovirus) proteomes by BLAST analysis. The B cell antigenicity indices are shown, and those above the server set threshold of 0.35 are in italics. The first column shows the amino acid number within the peptide or protein sequence, and the second shows the amino acid pertaining to that position. The alignments with pathogen proteins are shown. Spaces represent nonidentical amino acids and + signs amino acids with similar physicochemical properties. Only highly antigenic regions of pentapeptides or more were processed. The VGGVV sequence, antibodies to which label beta-amyloid in brain tissue, despite relatively low antigenicity, has already been reported to be identical to proteins expressed by 69 viruses including HSV-1, HSV-2, and HHV6.

(a)

Position B-Amy	Amino acid	B-cell index	Alignments
1	D	0.41	C. neoformans +AE HDSG+ Borrelia burgdorferi DAE F H+SG EV H. pylori DA FRH HSV-1 +AE RH HHV-6 D FR DS P. gingivalis +AEFR C. pneumoniae DA EFRHD and +AEFR +SG
2	A	0.35	C. neoformans AEFR D GY+V H. pylori AEF D S YE and AE+RH+ Borrelia burgdorferi AEF H+ Cytomagalovirus AEFR HD HSV-1 AE R SG HHV-6 AE+ HD P. gingivalis A+F H+S and AEFR C. pneumoniae AEF DSG
3	E	0.62	H. pylori EFRHD HHV-6 EF DSG Borrelia Burgdorferi EFR DS C. neoformans EF R DS YE P. gingivalis E R DSGY V C. pneumoniae EF SGYEV
4	F	0.73	C. neoformans FRHDS Borrelia burgdorferi +RH SGY++ and F H+SG H. pylori F HD EV Cytomegalovirus FR SGY P. gingivalis +RHDS C. Pneumonia F H+SGY
5	R	0.85	C. neoformans R D GYEV H. pylori RHDS Y V and R SGYE Borrelia burgdorferi RH+ GY Cytomegalovirus RHD YE and RHDSG HSV-1 RH SG HHV-6 RHDS P. gingivalis R+DS Y+
6	H	0.57	C. neoformans HDSGY H. pylori H. pylori +DSGY and HD G EV and HD EV Borrelia burgdorferi H+SG Y+V HSV-1 HDSG P. gingivalis HDSG C. pneumoniae ++SGY+V
7	D	0.69	C. neoformans DSGY+V H. pylori +SG+EV HSV-1 DSGY P. gingivalis DSG+EV C. pneumoniae DSGY V
8	S	0.38	P. gingivalis SGYEV H. pylori SGYE C. neoformans SGY++ C. pneumoniae SG+EV
9	G	0.63	H. pylori GYEVH Borrelia burgdorferi GYE V KL+ C. neoformans GYE LV and GY++ + LV P. gingivalis GYEV C. pneumoniae GYEV and GY HH
10	Y	0.56	H. pylori YE HH and YE+ HQ and Y++H Q and YE HHQ Cytomegalovirus YEVH Borrelia Burgdorferi YE+ KL C. neoformans YE + QK FC P. gingivalis Y++H H+K C. pneumoniae Y+V +Q LV
11	E	0.58	H. pylori EV +QK Cytomegalovirus EV HQ L Borrelia Burgdorferi EV +KL C. neoformans EV Q LV P. gingivalis EV KLV C. pneumoniae EV QKLV
12	V	0.35	H. pylori. +H QK Cytomegalovirus V HQ LV HHV-6 VH QK+V Borrelia Burgdorferi VH KL C. neoformans +HH LV P. gingivalis VH + LV C. pneumoniae V HQKL
13	H	−0.17	H. pylori and C. pneumoniae HHQK Cytomegalovirus HH KL P. gingivalis HH KL
14	H	−0.66	Borreli Burgdorferi HQKL+ C. pneumoniae and HSV-1 HQKL P. gingivalis +QKLV
15	Q	−1.03	C. neoformans and P. gingivalis and C. pneumoniae QKLV
16	K	−1.47	H. pylori: Cryptococcus neoformans Borrelia burgdorferi Chlamydophila pneumoniae KLVFF Human herpesvirus 1 KLVF
17	L	−1.34	Human herpesvirus 5: Human herpesvirus 6 LVFF
18	V	−1.20
19	F	−0.93
20	F	−0.98
21	A	−0.82
22	E	−0.31
23	D	0.23
24	V	0.81	Borrelia burgdorferi Cryptococcus neoformans Porphyromonas gingivalis VGSNK Cytomegalovirus +GSNK Helicobacter pylori Chlamydophila pneumoniae VGSN
25	G	1.24	H. pylori Chlamydophila pneumoniae GSNK
26	S	1.22
27	N	0.90
28	K	0.36
29	G	0.30
30	A	−0.24
31	I	−0.58
32	I	−1.00
33	G	−1.14
34	L	−1.19
35	M	−1.23
36	V	−1.16	69 viruses/phages VGGVV
37	G	−0.97
38	G	−1.02
39	V	−0.63
40	V	−0.45
41	I	−0.80
42	A	−1.06

(b)

NGF position	Amino acid	B-cell index	Alignment
18	A	0.59	C. neoformans AEPHS
19	E	1.16	P. gingivalis EPHSES—NVP Cytomegalovirus EPHS+S
20	P	1.32	C. neoformans P+S NVPAG and PHSES and P SESNV
21	H	1.78	Borrelia burgdorferi HSESN C. neoformans HSES VP and HSESN P H +P+
22	S	1.64	C. neoformans S+S VPAG T P Borrelia burgdorferi burgdorferi C. neoformans Chlamydophila pneumoniae P. gingivalis SESNV P. gingivalis S+SNVP C. pneumoniae SESNV A
23	E	1.68	C. neoformans ESNVP and ESNV AG
24	S	1.51	C. neoformans SNVPA
25	N	1.61	C. neoformans Cytomegalovirus P. gingivalis NVPAG C. neoformans NV TIPQA P. gingivalis +VPAG HT
26	V	1.45	C. neoformans P. gingivalis VPAGH C. neoformans VP AGHT C. neoformans VPAG TI and V AGHT+
27	P	1.36	C. neoformans HSV-1 PAGHT C. neoformans PAGHT P C. neoformans PAG TIP
28	A	1.04	C. neoformans H. pylori AGHTI C. neoformans AG H IPQA and AGHT PQ and AGHT+P and AG TIP HSV-1 HSV-2 AGH PQ and AGHT QA
29	G	1.00	C. neoformans GHTI Q and GHT PQ and G TIPQ
30	H	0.93	C. pneumoniae HTI QA C. neoformans HT PQA and HTIP A
31	T	1.05	C. neoformans P. gingivalis TIPQA
32	I	0.95
33	P	0.64
34	Q	0.41
35	A	0.46
51	A	0.38	C. neoformans AR SAPA and AR APAA and A SAPAA and ARSA AA and ARSAP A and ARS PAA and AR—SAPAA
52	R	0.54	HSV-1 RSAPAA Borrelia burgdorferi burgdorferri RSA AA
53	S	0.91	C. neoformans C. pneumoniae Cytomegalovirus HSV-1 HSV-2 P. gingivalis SAPAA
54	A	0.89
55	P	0.72
56	A	0.69
57	A	0.53
64	A	0.46	C. neoformans AG TRNI and AGQT RN and AGQTR P. gingivalis AGQTR
65	G	0.59	C. neoformans + RNITV and GQTRN
66	Q	0.42	P. gingivalis Borrelia burgdorferi QTRNI Cytomegalovirus QTRN—IT
67	T	0.43	C. neoformans P. gingivalis TRNIT
68	R	0.49	C. neoformans RNIT DP and RNITV
69	N	0.76	C. neoformans C. pneumoniae H. pylori NITVD
70	I	0.66
71	T	0.56
90	S	0.40	C. neoformans STQPPR and STQPP AA and STQPP EA C. pneumoniae STQ PRE C. pneumoniae Cytomegalovirus STQPP HSV-1 STQ PR
91	T	0.63	C. neoformans TQP REA and TQPPR
92	Q	1.06	C. neoformans QPPRE
93	P	1.49	C. neoformans PP REAA C Neoformans P. gingivalis PPREA
94	P	1.91	C. neoformans HSV-2 H. pylori PREAA
95	R	2.13	C. neoformans P. gingivalis REAAD and REAA TQ and RE ADT C. neoformans REAA DT and R AADT and R+AADT and READD HSV-1 REAA T Borrelia burgdorferi burgdorferi Cytomagalovirus RE ADT Cytomagalovirus REAA TQ P. gingivalis REA +TQ
96	E	2.13	P. gingivalis EAADTQ and EA TQDLD C. neoformans EAADT+ and EAAD QD and EAAD Q and EAA TQ
97	A	1.92	Borrelia burgdorferi burgdorferi C. neoformans AA TQD Borrelia burgdorferi burgdorferi P. gingivalis AAD QD HSV-2 AADT D HHV-6 AAD +DL C. neoformans AADT D and AA TQD and A DTQD and A TQDL and AADTQ and AADT+ D+D P. gingivalis ADTQ L H. pylori AADTQ
98	A	1.9	Borrelia burgdorferi ADT DLD C. neoformans AD QDLD and AD QDL P. gingivalis ADT DL and AD QDL H. pylori +TQDLD
99	D	1.39	C. neoformans DT DLD and D QDLD C. pneumoniae DTQDL
100	T	1.25	C. neoformans H. pylori P. gingivalis TQDLD
101	Q	0.66	Borrelia burgdorferi burgdorferi C. neoformans H. pylori P. gingivalis QDLDF H. pylori QD DFEV
102	D	0.73	Borrelia burgdorferi burgdorferi C. neoformans H. pylori DLDFE C. neoformans DLD EVG and DLDF VG
103	L	0.54	C. neoformans LD EVGG and LDFE GG and LDFEV and LDF VGG H. pylori LDF EVGG HSV-1 HSV-2 L+ EVGG
104	D	0.45	Borrelia burgdorferi burgdorferi DFEVG C. neoformans DF VGGA and D EVGGA
105	F	0.42	C. neoformans FEVGG Cytomegalovirus FE GGAA
106	E	0.49	C. neoformans EVGGAA and EVGGA P and EVGGA and EV GAAP and E+GGAAP H. pylori EVGGA Borrelia burgdorferi burgdorferi E+GG A PF+
107	V	0.39	P. gingivalis VGGAAP and VGGAA C. neoformans VGGAA PF and VGGAA NR and VGGAA and VG GAAP C. pneumoniae VGGA AP H. pylori VG GAAP and VGG APF and VGGAA P. gingivalis VGGAA
108	G	0.74	C. neoformans C. pneumoniae HSV-2 GGAAP
109	G	0.44	C. neoformans GA APFN T and GAAPF
110	A	0.95	C. pneumoniae AAPFN Borrelia burgdorferi AAP+NR HSV-1 AAP RT
111	A	0.83	C. neoformans APFN T RS C. neoformans H. pylori APFN TH C. pneumoniae AP N RT R RSSS
112	P	0.99	C. neoformans PFNRT and PF RTH Borrelia burgdorferi burgdorferi PF NRT
113	F	0.84	C. neoformans FNRT SKR
114	N	0.75	C. neoformans NR RSKRS S and NRT R RSSS Cytomegalovirus N T RSKRS
115	R	0.63	C. neoformans RT R SKRS and RTHRS Borrelia burgdorferi burgdorferi RTHRS
116	T	0.63	C. neoformans THRS RS and THRSK
117	H	0.64	C. neoformans HRS RSS and HRSKR C. Pneumonie HRSKR
118	R	0.94	C. neoformans RSKRSS and RS RSSS and RS KRSS and RS KRSS and RSK SSS and RSKRS S P. gingivalis RSKR S and RSKRS Borrelia burgdorferi burgdorferi RSKRS
119	S	0.88	C. neoformans SKRSSS and SKRSS C. pneumoniae H. pylori HSV-1 HSV-2 SKRSS
120	K	1.12	C. neoformans Cytomegalovirus HHV-6 H. pylori KRSSS
121	R	1.13
122	S	1.12
123	S	0.83
124	S	0.50
144	G	0.52	C. neoformans GDKTTA and GDKTT
145	D	0.54	H. pylori DK TATDI Borrelia burgdorferi burgdorferi C. neoformans C. pneumoniae H. pylori DKTTA HSV-1 +KTT TD
146	K	0.84	CF. Pneumoniae KTTAT+ C. neoformans H. pylori KTTAT
147	T	1.27	C. neoformans HSV-1 TTATDI C. neoformans P. gingivalis TTATD
148	T	1.22	C. neoformans TATDIK Borrelia burgdorferi burgdorferi C. neoformans C. pneumoniae H. pylori TATDI
149	A	1.21	C. neoformans HHV-6 HHV-6B P. gingivalis ATDIK
150	T	1.08
151	D	1.01
152	I	0.97
153	K	0.61
179	C	0.87	C. neoformans CR PNPV C. pneumoniae CRDPN P+ S RGI
180	R	1.40	C. pneumoniae RDPNPV Borrelia burgdorferi burgdorferi RD NP VDS C. neoformans RDP PVDS and RDPNP+ and RDPNP HHV-6 HHV-6B RDPNP HSV-1 HSV-2 RDPN V
181	D	1.36	Borrelia burgdorferi burgdorferi D NPVD and DPN VD C. neoformans DPNPV and DP PVD and DP PVDS and DPN VDS C. pneumoniae DPN VD HSV-1 DPNP S HSV-2 +P PVDS
182	P	1.69	C. neoformans PN VDSG and PNP DSG and PNPVD P. gingivalis PNPV+S and P PVDS
183	N	1.72	H. pylori NPVD G
184	P	1.85	C. neoformans PV DSGCR and P PVDS RG and PVDSG Cytomagalovirus P DSG RGI P. gingivalis PV DSGC
185	V	1.74	HSV-2 VDSG RG HSV-1 +DSG RG C. neoformans VDSG R
186	D	1.51	C. neoformans DSGC GI and DSG RG
187	S	1.28	Borrelia burgdorferi burgdorferi C. neoformans SGCRG and SG RGI and S CRGI
188	G	0.79	C. neoformans GC IDSKH W and GCRG D P. gingivalis GCRGI and GCRG+
189	C	0.79	P. gingivalis CRGID C. neoformans C GIDS
190	R	0.85	C. neoformans R IDSK and RGIDS and RGID K H. pylori RGIDS HSV-1 HSV-2 RG+DS H. pylori RG DSK Borrelia burgdorferi burgdorferi RGID K
191	G	0.65	C. neoformans GIDS HW and GIDSK and GIDS H Borrelia burgdorferi burgdorferi H. pylori P. gingivalis GIDSK P. gingivalis GID KH and G DSKH H. pylori GI SKH
192	I	0.60	Borrelia burgdorferi burgdorferi IDSKH C. neoformans P. gingivalis IDSK W
193	D	0.3	C. neoformans DSKH W Borrelia burgdorferi burgdorferi DSK WN
194	S	0.40	C. neoformans SKHW+
195	K	0.44
197	W	0.41
212	T	0.33	C. neoformans TMDGKQ and TMDGK
213	M	0.31	P. gingivalis MDGKQ
214	D	0.39	C. neoformans DGKQAA and DGKQA C. pneumoniae DGK AA
215	G	0.48	C. neoformans GKQAA
216	K	0.53
217	Q	0.45

(c)

Tau position	Amino acid	B-cell index	Alignment
53	E	2.516	C. neoformans (GSK3)EDGSEEP S and E+G EEPG and +DGS+EP S and ED GSEE GS and EDGS++ GS and EDGSE and +D EEPG and EDG S PGS Cytomagalovirus EDG EEP and +DG EE and ED GSEE P. gingivalis EDGSEE and E+G SEEP and EDGS EE HHV-6 HHV-6B EDGS EE C. pneumoniae E GSEE Borrelia burgdorferi E GSEE HHV-6 E GSEE
54	D	2.568	C. neoformans DGSEEP and DGS+EPG and DGSEE G P. gingivalis DGS EPGS and DGSEE and DGS EP and DGSE EP and DGSE P Cytomegalovirus DGS EP and DG EE G C. pneumoniae DGSE GS and +G EE GS Borrelia burgdorferi DGSE+ P. gingivalis +GSEE
55	G	2.621	C. neoformans GSEEP and G EEPG and G +EPGS and GS EEPG and GSEE G Cytomegalovirus GS+EP S P. gingivalis GS EPG H. pylori GSEE G C. pneumoniae GSEE GS
56	S	2.732	C. neoformans SEEPG and SEE GS and S EPGS and SEEP S C. pneumoniae SEEPG and SEE GS and SE PGS P. gingivalis SEE GS and S EPGS
57	E	2.774	C. neoformans EEPGS and +EPGS and EEPG E and EE GSE C. pneumoniae EEPGS HSV-1 HSV-2 EEPG
58	E	2.678	HHV-6 HHV-6B EPGSE C. neoformans EPGSE and EPGS+ P. gingivalis EPGS+
59	P	2.564
60	G	2.544
61	S	2.556
62	E	2.287
171	S	2.315	Borrelia burgdorferi SG GPED C. neoformans SG GPEDT and SGT PE and SGTGP and SG GPE and SGTG E and SG GP+ P. gingivalis SGTG E C. pneumoniae SGTG PE Cytomegalovirus SGTGP+
172	G	2.54	C. neoformans GT PED and GTG ED and GTGPE and G GPED and GTGP D and G EDTE HSV-1 GTGPE and GTGP D and GTGP+D HSV-2 GTGP D and G GPED C. pneumoniae GTGPE H. pylori GTGP D
173	T	2.731	HHV-6 TGPEDT and TG PEDT C. neoformans TG PEDT and TG EDT and T PEDT and TGPED C. pneumoniae TGPED H. pylori TG EDT Borrelia burgdorferi TGPE T+
174	G	2.709	C. neoformans GPEDT and GPED TE and GP DTE and GPED E HHV-6 HHV-6B TG PEDT
175	P	2.807	C. neoformans H. pylori P. gingivalis PEDTE
176	E	2.7
177	D	2.563
178	T	2.397
179	E	2.225
228	S	2.396	HSV-1 SP DSPP and SPQ SP C. neoformans SPQDS and S QDSP and SP DSPP and SP DSPP and SPQD PP and PQ DSPPS and SPQ PPSK and SPQ SP and SP DSP and SPQ SP Cytomegalovirus SP DSPP P. gingivalis SP DSP Borrelia burgdorferi SP++SPP and SP D PSK
229	P	2.744	C. neoformans PQ SPPS and P DSPPS and PQDSP and P+DSPP and PQ S PPSK and PQ SPP and PQD PP and P DSPP P. gingivalis PQDS P HSV-2 P DSPP HHV-6 PQ+ PP and PQ PP K Borrelia burgdorferi PQ+ P SK
230	Q	2.763	C. neoformans QDSPP and ++ PPSK and QDS PS and Q SPPS P. gingivalis QD PPS C. pneumoniae QDS PS
231	D	2.929	C. neoformans DSP PSK and DSPPS and DSP SK and D PPSK and +SPPS P. gingivalis DSP SK
232	S	2.882	C. neoformans SPPSK
233	P	2.75
234	P	2.794
235	S	2.68
242	D	2.387	C. neoformans DGRPP C. pneumoniae DG PPQ HSV-1 DG PPQ HSV-2 DGRPP and DG PP+ Cytomegalovirus DG R PQ and DG PP and +GRPP Borrelia burgdorferi DG PP
243	G	2.49	C. neoformans GRPPQ
244	R	2.56
245	P	2.42
246	P	2.164
247	Q	2.004
331	P	2.259	C. neoformans PGEG PE and P EGPEA and PGEGP and PGEG EA and P EGPEA and PGEG E Cytomegalovirus PGEGP EA and PG GPE C. pneumoniae PGE PEA and PGEGP H. pylori PG GPE HSV-1 HHV-6 PG GP A
332	G	2.681	C. neoformans GEGPE and GEG EA and GE PEA and G GPEA and GEGP A and GEG EA and G+GPEA C. pneumoniae GE PEA P. gingivalis GEGPE and GEG EA
333	E	2.715	C. neoformans P. gingivalis EGPEA HSV-2 +GPEA
334	G	2.634
335	P	2.592
336	E	2.463
337	A	2.405
414	H	1.819	HSV-1 HSV-2 HPTPG C. neoformans HPT GSS and HP PGSS and HPTP SS and HP P SS C. pneumoniae HP PGS and +PT SS
415	P	2.274	Cytomegalovirus P PGSS and PTPG SS C. pneumoniae PT GSS and PTPG SS
416	T	2.503
417	P	2.717
418	G	2.469
419	S	2.054
420	S	1.76
493	P	2.43	HSV-1 P APKTP and P APKTP and PPAP PP and PPA PP HSV-2 PPAP TPP Cytomegalovirus P APKT and PPAP PP and PP P PPS and PP KTPP and PP A TPPS and PPA TPP C. neoformans PPAP TPPS and PPAP KTP S and PP PKTP and PP PKTP and PPAPKT and PPAP KT P. gingivalis PPAPK P C. pneumoniae PPAPK and PP PKT and PP AP PP and PP TPP Borrelia burgdorferi PAP T PS and PPA KTP and PP P TPP
494	P	2.77	HSV-1 PAP KTP and PA KTPP HSV-2 PAPK PP HHV-6 PAP PPS C. neoformans PAPKTP S and PAPK PP P. gingivalis PAPKT C. pneumoniae PAP TP and PAPK P
495	A	2.94	C. neoformans AP PPS P. gingivalis A KTPPS HHV-6 APKTP
496	P	2.89	C. neoformans PKTPPS and PKTP PS and PK TPPS P. gingivalis PKT PS
497	K	2.95	C. neoformans KTPPS
498	T	2.98
499	P	2.69
500	P	2.51
501	S	2.343
502	S	2.123