On 2016 May 29, Claudiu Bandea commented:

Remarkable results, questionable report

“Our findings raise the intriguing possibility that β-amyloid may play a protective role in innate immunity and infectious or sterile inflammatory stimuli may drive amyloidosis” (1). Indeed, fascinating findings. What Kumar et al. did not articulate, though, is that their result is one of many findings, observations, and arguments supporting the theory (2,3) that:

(i) β-amyloid, tau, α-synuclein, huntingtin, TDP-43, prion protein and other primary proteins implicated in neurodegenerative diseases are members of the innate immune system;

(ii) The isomeric conformational changes of these proteins and their assembly into various oligomers, plaques, and tangles are not protein misfolding events as defined for decades, nor are they prion-replication activities, but part of their normal, evolutionarily selected innate immune repertoire;

(iii) The immune reactions and activities associated with the function of these proteins in innate immunity lead to Alzheimer’s, Parkinson’s, Huntington’s, ALS and Creutzfeldt-Jakob Disease, which are innate immunity disorders.

Generating data and observations, although essential, represents only half of the scientific process; the other is their interpretation and integration into the existing knowledge and paradigms. That’s where the article by Kumar et al. falls short.

Perhaps the authors were not fully familiar with the literature and paradigms in the field of neurodegenerative diseases. Or, perhaps, Kumar et al. did not consider it relevant to discuss their results in the context of previous findings, ideas and hypotheses. For example, the authors did not address or explain their results in context of the ‘prion’ paradigm, which has dominated the thinking in the field of Alzheimer’s and other neurodegenerative diseases in the last few years (e.g. 4-7). Nor did they refer to a related study entitled “Alpha-synuclein expression restricts RNA viral infections in the brain” (8), which is highly relevant considering the fact that alpha-synuclein, a putative member of the innate immune system and the primary protein implicated in Parkinson’s, is a significant player in Alzheimer’s disease. Also, some might consider highly questionable leaving out the study by Kobayashi et al. entitled “Binding sites on tau proteins as components for antimicrobial peptides” (9).

Given these omissions, it's no wonder in her The New York Times article on Kumar et al. study, Gina Kolata wrote: “The Harvard researchers report a scenario seemingly out of science fiction”.

References:

(1) Kumar et al. 2016. Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer's disease. Sci Transl Med. 25;8(340); Kumar DK, 2016

(2) Bandea CI. 2013. Aβ, tau, α-synuclein, huntingtin, TDP-43, PrP and AA are members of the innate immune system: a unifying hypothesis on the etiology of AD, PD, HD, ALS, CJD and RSA as innate immunity disorders. bioRxiv. doi: 10.1101/000604; http://biorxiv.org/content/biorxiv/early/2013/11/18/000604.full.pdf

(3) Bandea CI. 2009. Endogenous viral etiology of prion diseases. Nature Precedings; http://precedings.nature.com/documents/3887/version/1/files/npre20093887-1.pdf

(4) Frost B, Diamond MI. 2010. Prion-like mechanisms in neurodegenerative diseases. Prion. 1(3):155-9; Frost B, 2010

(5) Nussbaum JM, Seward ME, Bloom GS. 2013. Alzheimer disease: a tale of two prions. Prion. 7(1):14-9; Nussbaum JM, 2013

(6) Watts JC et al. 2014. Serial propagation of distinct strains of Aβ prions from Alzheimer's disease patients. Proc Natl Acad Sci U S A. 11(28):10323-8; Watts JC, 2014

(7) Jaunmuktane et al. 2015. Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy. Nature. 525:247-50; Jaunmuktane Z, 2015

(8) Beatman et al. 2015. Alpha-Synuclein Expression Restricts RNA Viral Infections in the Brain. J Virol. 90(6):2767-82; Beatman EL, 2015

(9) Kobayashi et al. 2008. Binding sites on tau proteins as components for antimicrobial peptides. Biocontrol Sci. 13(2):49-56. Kobayashi N, 2008

(10) Kolata G. 2016. Could Alzheimer’s Stem From Infections? It Makes Sense, Experts Say. The New York Times; May 25, 2016.http://www.nytimes.com/2016/05/26/health/alzheimers-disease-infection.html?_r=0

On 2016 May 29, Claudiu Bandea commented:

Remarkable results, questionable report

“Our findings raise the intriguing possibility that β-amyloid may play a protective role in innate immunity and infectious or sterile inflammatory stimuli may drive amyloidosis” (1). Indeed, fascinating findings. What Kumar et al. did not articulate, though, is that their result is one of many findings, observations, and arguments supporting the theory (2,3) that:

(i) β-amyloid, tau, α-synuclein, huntingtin, TDP-43, prion protein and other primary proteins implicated in neurodegenerative diseases are members of the innate immune system;

(ii) The isomeric conformational changes of these proteins and their assembly into various oligomers, plaques, and tangles are not protein misfolding events as defined for decades, nor are they prion-replication activities, but part of their normal, evolutionarily selected innate immune repertoire;

(iii) The immune reactions and activities associated with the function of these proteins in innate immunity lead to Alzheimer’s, Parkinson’s, Huntington’s, ALS and Creutzfeldt-Jakob Disease, which are innate immunity disorders.

Generating data and observations, although essential, represents only half of the scientific process; the other is their interpretation and integration into the existing knowledge and paradigms. That’s where the article by Kumar et al. falls short.

Perhaps the authors were not fully familiar with the literature and paradigms in the field of neurodegenerative diseases. Or, perhaps, Kumar et al. did not consider it relevant to discuss their results in the context of previous findings, ideas and hypotheses. For example, the authors did not address or explain their results in context of the ‘prion’ paradigm, which has dominated the thinking in the field of Alzheimer’s and other neurodegenerative diseases in the last few years (e.g. 4-7). Nor did they refer to a related study entitled “Alpha-synuclein expression restricts RNA viral infections in the brain” (8), which is highly relevant considering the fact that alpha-synuclein, a putative member of the innate immune system and the primary protein implicated in Parkinson’s, is a significant player in Alzheimer’s disease. Also, some might consider highly questionable leaving out the study by Kobayashi et al. entitled “Binding sites on tau proteins as components for antimicrobial peptides” (9).

Given these omissions, it's no wonder in her The New York Times article on Kumar et al. study, Gina Kolata wrote: “The Harvard researchers report a scenario seemingly out of science fiction”.

References:

(1) Kumar et al. 2016. Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer's disease. Sci Transl Med. 25;8(340); Kumar DK, 2016

(2) Bandea CI. 2013. Aβ, tau, α-synuclein, huntingtin, TDP-43, PrP and AA are members of the innate immune system: a unifying hypothesis on the etiology of AD, PD, HD, ALS, CJD and RSA as innate immunity disorders. bioRxiv. doi: 10.1101/000604; http://biorxiv.org/content/biorxiv/early/2013/11/18/000604.full.pdf

(3) Bandea CI. 2009. Endogenous viral etiology of prion diseases. Nature Precedings; http://precedings.nature.com/documents/3887/version/1/files/npre20093887-1.pdf

(4) Frost B, Diamond MI. 2010. Prion-like mechanisms in neurodegenerative diseases. Prion. 1(3):155-9; Frost B, 2010

(5) Nussbaum JM, Seward ME, Bloom GS. 2013. Alzheimer disease: a tale of two prions. Prion. 7(1):14-9; Nussbaum JM, 2013

(6) Watts JC et al. 2014. Serial propagation of distinct strains of Aβ prions from Alzheimer's disease patients. Proc Natl Acad Sci U S A. 11(28):10323-8; Watts JC, 2014

(7) Jaunmuktane et al. 2015. Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy. Nature. 525:247-50; Jaunmuktane Z, 2015

(8) Beatman et al. 2015. Alpha-Synuclein Expression Restricts RNA Viral Infections in the Brain. J Virol. 90(6):2767-82; Beatman EL, 2015

(9) Kobayashi et al. 2008. Binding sites on tau proteins as components for antimicrobial peptides. Biocontrol Sci. 13(2):49-56. Kobayashi N, 2008

(10) Kolata G. 2016. Could Alzheimer’s Stem From Infections? It Makes Sense, Experts Say. The New York Times; May 25, 2016.http://www.nytimes.com/2016/05/26/health/alzheimers-disease-infection.html?_r=0