George Perry and Mark A. Smith led this live discussion on 14 August 2001. Readers are invited to submit additional comments by using our Comments form at the bottom of the page.

View Transcript of Live Discussion — Posted 30 August 2006

Background Text
By George Perry and Mark A. Smith

Use of standard language is essential to convey ideas with the least encumbrance of misunderstanding. To this end, the amyloid field has the Amyloid Nomenclature Committee whose recommendations have been approved by the World Health Organization (1). Unfortunately, their recommendations (2), namely amyloid-β (Aβ) and Aβ protein precursor (AβPP), have not been broadly adopted by those who study Alzheimer disease. Variations in the nomenclature used to describe amyloid-β and its precursor include A4, βA, AP, APP, βPP, βAPP, AβPP and others. It would assist readers, and certainly editors of journals, if the field could adopt an accepted nomenclature for Aβ/AβPP and other phenomena relevant to Alzheimer disease. To this end, we propose that there be a discussion following a poll to hopefully establish a nomenclature that is accepted by the AD field.

(1993) Nomenclature of amyloid and amyloidosis. WHO-IUIS nomenclature sub-committee. Bull WHO Health Organization 71, 105-108. Abstract.

(1999) Westermark P, Araki S, Benson MD, Cohen AS, Frangione B, Masters CL, Saraiva MJ, Sipe JD, Husby G, Kyle RA, Selkoe D. Nomenclature of amyloid fibril proteins: Report from the meeting of the International Nomenclature Committee on Amyloidosis, August 8-9, 1998. Amyloid: Int J Exp Clin Invest 6, 63-66. View PubMed record..

Q. Is the failure by the field to adopt standard nomenclature the result of philosophical differences, or just ignorance or sloppiness (to which I plead guilty)? If the former, then it could be productive to have a discussion of the rationales for preferring one terminology over another, and to conduct a poll. If the latter, the solution would be to educate researchers in correct usage. We could issue a style sheet to journal editors, which would be given to authors. I'll begin right here on the ARF by adopting the WHO-approved nomenclature and carrying out a search and replace mission on all outlawed forms. (But someone will have to show me how to type Greek letters!)—June Kinoshita.

A. My opinion is that the failure to adopt a standard nomenclature is the result of an indifference to the need for uniformity of terms. Your approach to have a discussion and a poll may finally lead to a nomenclature that all can adopt.

Comment by Robert Kisilevsky—Posted 9 January 2001
The use of APP (amyloid precursor protein) by the "Alzheimer" research community is most unfortunate as there are about 25 different amyloid precursor proteins (APPs) at least half of which were discovered before the Alzheimer's form. To claim this general name for the Alzheimer's form is at best inappropriate and confusing. My preference (beta-protein) is the term coined by George Glenner who was the first to identify this protein. Thus the precursor becomes the beta-precursor protein or betaPP. Abeta is also acceptable (but is a compromise) in which case the precursor is designated AbetaPP.

Comment by Merrill Benson—Posted 15 January 2001
The recommendation by the Amyloidosis Nomenclature Committee to use Abeta for the fibril protein and AbetaPP for the precursor was a compromise that seemed good at the time. It still seems a good idea. The suggestion to strongly recommend that journals use this designation may help resolve the issue.

Comment by Juan F. Gomez-M—Posted 16 March 2001
Theoretical work about nomenclature is essential in any mature (?) discipline. But to develop an "axiomatic discourse" (hopefully, something with some superficial similarity to the Euclides'work on geometry!) we have to define the "primitives." It seems, however, that there are still problems in the basic definitions. Dr. Ming Chen propose fundamental differences between AD and senile dementia. Is this a condition or a disease? If we still do not agree about it, how we can agree about the name of a molecule (Presenilin, gamma-secretase) or its precursors (APP, betaPP or AbetaPP)?

To make the things more confusing, these proteins are also involved in normal function and neurogenesis. The problem can produce in the long-term skepticism and a crisis in AD research: a collection of opinions instead of well-defined facts. Clear building-block concepts is fundamental to construct databases with the fundamental facts, and it is important that the researchers answer those questions "before the literature base becomes much larger" (Dr. Norris). Moreover, thousands of dollars in experiments can have a better use if we know more precisely about what is exactly what we are researching. This discussion deserves more attention.

Comment by Colin L Masters and Konrad Beyreuther—Posted 13 August 2001
While the International Committee on Amyloidosis has grappled with the complexities of unifying a disparate field, its conclusions relating to the proteins which accumulate in the two most important diseases [Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD)] are at variance with current usage.

In AD, APP is widely recognised as the precursor of Ab amyloid. This nomenclature allows for the designation of the a- and b-secretase products (APPa, APPb) whereas the proposed AbPP makes these extremely confusing. The alternate splice products (L-APP, APP-KPI, etc) are manageable, and the related family members (APLP 1, 2; APPL, etc) are easily accommodated. We suggest the APP be taken to mean "Alzheimer Precursor Protein", and thereby avoid the difficulties perceived in the Committee's deliberations.

In CJD, the PrP protein nomenclature is established, with a superscript to denote the various subtypes (Sc, CJD, GSS, FFI, etc). At which stage the normal cell product (PrPc) converts into the protease-resistant/b-sheet-enriched conformer, and then progresses eventually into a polymerised PrP amyloid fibril, is not fully understood. To indicate that APrPSc should be used for all categories of PrP other than PrPc is clearly problematic.

Finally, the Committee's decision to exclude all intracellular aggregates with the histochemical and other properties of amyloid is not helpful. These intracellular aggregates (and their precursors) may yet prove far more relevant in disease causation than extracellular accumulations. Amyloidologists are not doing themselves a favor by relegating them to the "too hard basket."

	Comments on Live Discussion
	Comment by:  David Teplow
	Submitted 17 November 2000  |  Permalink	Posted 17 November 2000
	There is nothing that upsets me faster than scientists using inappropriate and imprecise terminology and nomenclature. With respect to the Alzheimer's disease lexicon, the WHO and the International Nomenclature Committee on Amyloidosis have ALREADY dealt with this issue. I refer you to Bull. WHO 71:105-108 (1993) and Amyloid: Int. J. Exp. Clin. Invest. 6:63-66 (1999). You may also get a kick out a recent short commentary I wrote concerning the suggestion of altering the amyloid term itself (see Teplow Neurobiol. Aging 21:563-564 (2000)). The issues of BACE, gamma-secretase, etc., does need clarification. View all comments by David Teplow
	Comment by:  David O. Norris
	Submitted 17 November 2000  |  Permalink	Posted 17 November 2000
	Yes, at least some consensus would be appreciated, especially for people new to this field. For example, at the recent Neuroscience meeting in New Orleans, people were hedging on the latter case (presenilin-1 or gamma- secretase?) even to the extent of questioning whether or not they are the same protein. And then what about beta-secretase? And there should be agreement on the abbreviations used as well. A position statement from somewhere on this terminology indeed would be welcome before the literature base becomes much larger. View all comments by David O. Norris
	Comment by:  Bart De Strooper, ARF Advisor
	Submitted 29 January 2001  |  Permalink	Posted 29 January 2001
	I agree that it would be useful to accept a uniform nomenclature. For instance literature searches in Pub med would be more efficient. Sloppiness is probably the most important reason for the current situation and the forum is a good place to discuss the problem. The beta-symbol is a problem in electronic documents. A good starting point for the discussion would be a proposal not only for A-beta-PP, but also for the presenilins in different species, and the mutations. Also the different rules for protein or genes in different species (capitals or not, italics or not, etc.) is a problem. I am not very good in those things, but maybe you can ask somebody to make a proposal. Once there is some consensus I will certainly use the nomenclature in all next papers from my laboratory. View all comments by Bart De Strooper
	Comment by:  Ming Chen
	Submitted 21 February 2001  |  Permalink	Posted 21 February 2001
	Question: Are Alzheimer's Disease and "Senile Dementia" the Same Disease? This perhaps is the most important "nomenclature" problem. AD used to refer to "pre-senile" dementia (PSD; middle age dementia). This name clearly distinguished it from senile dementia (SD; dementia after age 60). However, since 1970s, they are redefined as the same disease (AD), mainly because they have the same symptoms and same hallmarks (plaques and tangles). This definition is the basis for AD research today. However, it recently came to our attention that if PSD/AD and SD are the same disease, then it would be difficult to explain: 1. After intensive studies, it has been confirmed that AD does exist in two major forms: early-onset and late-onset, corresonding essentially to PSD and SD. 2. Most PSD has been successfully linked to gene mutations, head injury and other severe insults, but SD remains largely as a mystery. If they are the same disease, then they should have the same causes (like AIDS). 3. While PSD remains a rare disease in the middle age people today, SD...  Read more Question: Are Alzheimer's Disease and "Senile Dementia" the Same Disease? This perhaps is the most important "nomenclature" problem. AD used to refer to "pre-senile" dementia (PSD; middle age dementia). This name clearly distinguished it from senile dementia (SD; dementia after age 60). However, since 1970s, they are redefined as the same disease (AD), mainly because they have the same symptoms and same hallmarks (plaques and tangles). This definition is the basis for AD research today. However, it recently came to our attention that if PSD/AD and SD are the same disease, then it would be difficult to explain: 1. After intensive studies, it has been confirmed that AD does exist in two major forms: early-onset and late-onset, corresonding essentially to PSD and SD. 2. Most PSD has been successfully linked to gene mutations, head injury and other severe insults, but SD remains largely as a mystery. If they are the same disease, then they should have the same causes (like AIDS). 3. While PSD remains a rare disease in the middle age people today, SD rate has increased exponentially and surpassed 50% after age 90. This makes SD in sharp contrast to conventional diseases (no more than a few percent). If they are the same disease, then why does one increase so much, but the other not? So, while it is usually correct to define diseases by pathologies but not by patients'ages (like AIDS or influenza), is it also correct for AD? View all comments by Ming Chen
	Comment by:  Ming Chen
	Submitted 15 August 2001  |  Permalink	Posted 15 August 2001
	Clarification of the confusing terms such as Aβ, βA, APP, βAPP or AβPP will help the field if they can be standardized. But here, I would like to reiterate the key importance of another "nomenclature" problem, i.e., "Alzheimer's disease" or "senile dementia"? The latter condition had been known since ancient time, but the former was defined by Dr. Alois Alzheimer in a 56-year-old patient. Dr. Alzheimer considered such rare cases as "pre-senile" or "midlife" dementia thus quite different from "senile dementia". So, the term "Alzheimer's disease" was defined mainly on the basis of its onset age difference from senile dementia. But since 1970s, the two conditions have been re-defined as the "same disease" on the rationale that they both exhibit the same symptoms...  Read more Clarification of the confusing terms such as Aβ, βA, APP, βAPP or AβPP will help the field if they can be standardized. But here, I would like to reiterate the key importance of another "nomenclature" problem, i.e., "Alzheimer's disease" or "senile dementia"? The latter condition had been known since ancient time, but the former was defined by Dr. Alois Alzheimer in a 56-year-old patient. Dr. Alzheimer considered such rare cases as "pre-senile" or "midlife" dementia thus quite different from "senile dementia". So, the term "Alzheimer's disease" was defined mainly on the basis of its onset age difference from senile dementia. But since 1970s, the two conditions have been re-defined as the "same disease" on the rationale that they both exhibit the same symptoms and same hallmarks. According to this new definition, senile dementia should be caused by similar pathogens that are known today to underlie pre-senile dementia such as gene mutations, vascular diseases or other severe insults. But, is this definition correct? We know that vision, hearing, or heart failures can also strike juvenile or middle-aged persons in rare cases, and these are certainly caused by inherited or invading pathogenic factors. But if the "same" failures occur in VERY OLD people, are they also due to the same factors? Yet, juvenile-onset cataracts (lens protein deposition) can affect young people in rare cases which have exactly the same symptoms and hallmarks of SENILE cataracts. Do we, therefore, believe that they have the same underlying causes? Failure of a new or middle-aged car is apparently due to manufacture error or accident, but is the eventual failure of a VERY OLD car or its parts also due to the same reasons? If they are not but officially defined as such, then what will happen to our investigations which are desperately looking for the cause of mainly the LATE-ONSET sporadic dementia because only this type of dementia has a horribly high prevalence and thus threats society the most today? The AD research field may need to face these difficult questions. Very recently, we have discussed them in more details (Ref. 1). References: 1. Chen, M., Fernandez, H.L. Alzheimer movement re-examined 25 years later: is it a "disease" or a "senile condition" in medical nature? Front. Biosci. 2001; 6, e30-40 (free full text): http://www.bioscience.org/2001/v6/e/chen2/fulltext.htm View all comments by Ming Chen

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