Defining neurodegenerative diseases
BMJ 2002; 324 doi: https://doi.org/10.1136/bmj.324.7352.1465 (Published 22 June 2002) Cite this as: BMJ 2002;324:1465All rapid responses
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In our
view defining neurodegenerative diseases is much more complicated as defining
the continent of Europe (BMJ
2002;324:1465-1466). May be a planet. But likely a universe
and not "after responsible rogue proteins". Why? Because we have significant
overlap of the involvement of different proteins in different neurodegenerative
disorders [ 1 ].
The reason could be simple. While making us humans planet brain operates
the standard set of basic tools such as neurotransmission, synaptic function,
neural plasticity, etc (largely missed in the discussion of the BMJ
theme issue editorials). The proteins named under the "evolving terminology"
statement of the editorial
by Williams (including amyloid beta [ 2 ], tau
[ 3 ], and superoxide dismutase 1 (SOD1) [ 1, 2
]) represent essential (normal and not pathological) elements of the brain/neuron
self maintanance and function. Infact, in 1999 we knew about more than one hundred
such elements [ 4 ]).
When the function fail the above proteins (and surely many others) react
in an organized compensatory way to fix the function, although the proportion
of the involevement and the particular compensatory reaction target (see
Ref.
2 for further discussion) could be different for different proteins
and for different brain neurotransmitter systems involved.
the definition of neurodegenerative diseases. Not convinced? Learn about the sad prime example of the simplification that just become the history [ Ref. 5 ]. |
Competing interests: none
References:
1. Koudinov AR, Koudinova NV,
Beisiegel U. Cholesterol disbalance at neuromuscular junctions and CNS
synapses: a unifying cause of degeneration. Neurology. Published
online 26 February 2002 [ Full
Text ]; Dunnett AB, Bjorklund A. Prospects for new restorative and
neuroprotective treatments in Parkinson disease. Nature. Neurological
disorders.399 (Supplement), A32-A39 (1999). Please
make a note of the Box 2 entitled: "Is PD a distinct clinical entity
or part of a spectrum of neurodegenerative disorders?" [ PubMed
].
2. Koudinov AR, Koudinova NV.
Brain Cholesterol Pathology is the Cause of Alzheimer's Disease. Clin
Med Health Res. published online November 27, 2001, clinmed/2001100005
[ Full
Text ] [ Authors
Preface ].
3. Koudinov AR, Koudinova NV.
Alzheimer's pathogenesis: tau and amyloid - a consensus or a challenge
for a third party quest? BMJ. Published online 4 September, 2001
[ Full Text
].
4. Sanes JR, Lichtman JW. Can
molecules explain long-term potention? Nature Neurosci.2,
597-604 [
PubMed ].
5. Koudinov AR, Smith MA, Perry
G, Koudinova NV. Alzheimer’s amyloid dogma. A time for change. BMJ.
Published online 21 June, 2002 [ Full
Text ]; Koudinov AR, Koudinova NV. What biomedical scientists and clinical
audience have to know is not what top journals offer to read. BMJ.
Published online 23 June, 2002 [ Full
Text ] [ list
of BMJ eLetters by Koudinov et al ] [ Other
related eLetters ]
a Colleague] [Send us an email] [Authors Internet Office] Search PubMed for: [ AR Koudinov | NV Koudinova ] |
Competing interests: No competing interests
Is neurodegeneration a unique multifarious human brain disease?
a Colleague
We realized
that it will be difficult for readers to find the article by Dunnett and
Bjorklund (in Nature Neurological disorders supplement issue [ 1
]) that we refer to in one [ 2 ] of the related
letters to BMJ [ 2, 3;
please see these letters first ].
There is the box 2 (in the above article [ 1
]) entitled "Is PD a distinct clinical entity or part of a spectrum of
neurodegenerative disorders?". We cite this box message below, and believe
that it will provide additional arguments against the simplification
in defining neurodegenerative disorders.
The box 2 of the article by Dunnett and Bjorklund
[ 2 ] states:
and Alzheimer's disease (AD) are generally considered to be separate and
distinct clinical entities, with PD involving predominantly motor symptoms
associated with loss of dopamine neurons and Lewy-body pathology in the
substantia nigra, and AD characterized by manifest cognitive symptoms associated
with neurofibrillary tangles (tau) and senile plaques (amyloid-b
protein), and primarily affecting cortical areas of the forebrain (see
review by Selkoe, this supplement). Nevertheless, there has been increasing
recognition that the two diseases overlap4.
Thus, a substantial proportion of PD patients show cognitive impairments,
particularly on tasks of executive function, similar to those seen after
frontal-lobe damage99. The incidence
of dementia in PD patients is 6-12 times higher than in age-matched controls,
and most of these (about 75%) have cortical pathology cheracteristic of
AD. Concersely, about two-thirds of diagnosed AD patients develop extrapyramidal
symptoms, such as bradykinesia and rigidity, and many have neurodegenerative
changes in the substantia nigra consistent with the diagnosis of PD. The
extent of overlap between the two diseases is thus much greater than would
be expected to occur by chance4.
Consequently,
we need to consider whether the two diseases may not be distinct entities,
as generally considered, but rather be extremes of a spectrum of disease.
Perl and colleagues4 propose that
PD and AD should be viewed as part of continuum of neurodegenerative disorders
with considerable overlap (see inset). Patients with
similar pathology, involving both Lewy bodies in the substantia nigra and
senile plaques and neurofibrillary tangles in the neocortex, are as likely
to be diagnosed as 'AD with parkinsonism' as 'PD with dementia'. Alternatively,
if both classes of symptom are apparent at first appearance, the diagnosis
may be 'diffuse Lewy-body disease' or 'Lewy-body dementia'4.
This emerging concept suggests that multiple aetiologies can lead to similar
clinical phenotypes, and that there may exist unifying neurodegenerative
mechanism(s), triggered by different aetiological factors, that are expressed
differently in different disease entities. Thus, in future research on
pathogenesis and treatment, it may be important to consider not only overlaps
between the major neurodegenerativee diseases, but also heterogeneous aetiologies
within each disease entity"
The above box has inset at the bottom. Our description
of the inset follows:
are several text labels at the bottom of the inset scheme. This text line
lists (from left to the right): Parkinson's disease, Parkinson's disease
with dementia, Diffuse Lewy body disease, Lewy body dementia, Alzheimer's
disease with parkinsonism, and finally Alzheimer's disease. Just above
this line with the diseases list there is a simple line drawing that has
a text labeling at the margins. The labels are 'Lewy body pathology' and
'Neurofibrillary pathology' on the left and right, respectively.
Simple
line drawing shows: i) the increase of the Neurofibrillary pathology
in the diseases ordered above, from zero in Parkinson's disease to maximal
in AD, and ii) the increase of the Lewy body pathology in
the diseases back ordered above, from zero in Alzheimer's disease to maximal
in PD.
To add to the cited above excellent writing by Dunnett and Bjorklund
[ 1 ] we would like to highlight the overlap
in the hallmarks of two other pairs of the neurodegenerative diseases.
These pairs are Alzheimer's/inclusion-body myositis and Alzheimer's/ALS,
jointly characterized by amyloid and tau abnormalities, respectively (see
also Ref. 5 ]. It is important to note that reactions
of oxidative cascade are also impaired in the above mentioned pathologies,
as well as in Parkinson's disease.
We also would like to invite readers to review
the online record for one of live discussions conducted by AlzForum.
This discussion pointed to an inability of 'amyloid deposits as the key
diagnostic Alzheimer's feature' to meet today knowledge and current fields'
needs.
definition of neurodegenerative diseases.
Not convinced? Learn about the sad prime example
of the simplification that just become the
history"
Koudinov & Koudinova BMJ online,
24 June 2002
Competing interests: none
References:
1. Dunnett AB, Bjorklund
A. Prospects for new restorative and neuroprotective treatments in Parkinson
disease. Nature. Neurological disorders. (suppl).399,
A32-A39 (1999) [ PubMed
].
2. Koudinov AR, Smith
MA, Perry G, Koudinova NV. Alzheimer’s amyloid dogma. A time for change.
BMJ. Published online 21 June, 2002 [ Full
Text ]; Koudinov AR, Koudinova NV. What biomedical scientists and clinical
audience have to know is not what top journals offer to read. BMJ.
Published online 23 June, 2002 [ Full
Text ] [ list
of BMJ eLetters by Koudinov et al ] [ Other
related eLetters ]
3. Koudinov AR, Koudinova
NV. Beware the simplification in defining neurodegenerative diseases. BMJ.
Published online 24 June, 2002 [ Full
Text ]
are two references from the grey-box citation (see above
and Ref.1)
4.
Perl DP, Olanow CW, Calne DB. Alzheimer's disease and Parkinson's disease;
distinct entities or extremes of a spectrum of neurodegeneration? Ann
Neurol. (suppl).44, S19-S31 (1998) [ PubMed
];
99.
Owen AM, Sahakian BJ, Robbins TW. in Memory in Neurodegenerative Disease:
Biological, Cognitive and Clinical Perspectives (ed.Trosyter AI) 157-171
(Cambridge Univ. Press, Cambridge, 1998).
5. Koudinov AR, Koudinova
NV, Beisiegel U. Cholesterol disbalance at neuromuscular junctions and
CNS synapses: a unifying cause of degeneration. Neurology. Published
online 26 February 2002 [ Full
Text ]; Koudinov AR, Koudinova NV. Alzheimer's pathogenesis: tau and
amyloid - a consensus or a challenge for a third party quest? BMJ.
Published online 4 September, 2001 [ Full
Text ].
a Colleague] [Send
us an email]
[Authors
Internet Office]
Search PubMed for:
[ AR
Koudinov | NV
Koudinova ]
Competing interests: No competing interests