Ruminations On a Technical Paper (Morton Pollycove)

Rumble B, et al. Amyloid A4 protein and its precursor in Down’s syndrome Alzheimer’s disease. N Engl J Med. 320:1446, 1989.

Abstract: In patients with Alzheimer’s disease, amyloid fibrils that are aggregates of A4 protein subunits are deposited in the brain. A similar process occurs at an earlier stage in persons with Down’s syndrome. To investigate the deposition of amyloid in these diseases, we used a radioimmunoassay to measure levels of the amyloid precursor (PreA4) In the serum of 17 patients with Down’s syndrome, 15 patients with Alzheimer’s disease, and 33 normal elderly controls.

The mean (+/- SD) concentration of serum PreA4 was increased 1.5-fold in patients with Down’s syndrome…. as compared with that in controls; the levels in patients with Alzheimer’s disease were similar to those in controls. We also found that the concentration of PreA4 in the brain tissue of two adults with Down’s syndrome (100 and 190 pmol per gram) was higher than in the brain tissue of either 26 patients with Alzheimer’s disease (64.4 +/- 17.3 pmol per gram) or 17 elderly controls with neurological disease (68.5) …. immunocytochemical studies of brain tissue from 26 patients with Down’s syndrome showed that the deposition of A4 protein amyloid began in these patients approximately 50 years earlier than it began in 127 normal aging subjects studied previously, although the rate of deposition was the same.

We conclude that, since the gene for PreA4 is on the long arm of chromosome 21, which is present in triplicate in Down’s syndrome, overexpression of this gene may lead to increased levels of PreA4 and amyloid deposition in Down’s syndrome. However, since increased levels of PreA4 are not present in Alzheimer’s disease, additional factors must account for the amyloid deposition in that disorder.

I. The Journal’s Abstract, Suitably Condensed
In patients with Alzheimer’s disease
amyloid fibrils that are aggregates
of A4 protein subunits are
deposited in the brain.

A similar process occurs at an earlier age
in persons with Down’s syndrome. To
investigate the deposition of
amyloid in these diseases,

we used a radioimmunoassay to measure
levels of the amyloid precursor (PreA4)
in the serum of 17 patients
with Down’s syndrome….

We conclude that….overexpression
of this gene may lead to increased levels
and amyloid deposition in Down’s.
However, since

increased levels of PreA4 are not
present in Alzheimer’s disease
additional factors must account. …
for that disorder.

II. The Newspaper Version
The thought police have invaded the ectodomains
of preA4. They have built roadblocks and
searched the the trains
for static movements which might miss
the numbers carved on a boomerang
by eight et als and Kang
in a code of blot analysis.

And they have found the traitors, the saboteurs,
the Congo reds, the argyrophilic conspirators.
They are standing now under bare bulbs
devoid of neuritic change, confessing
to genetic overexpressing.

667 to 676 drop chins in a hangdog cluster.
They have arrested Creutzfeldt-Jacob, Straussler,
and Gerstmann who meant to tile
our temporal roofs with amyloid.
Epitope CT-II is void
and awaiting trial.

All have been taken except for
the spymaster and his receptor
who successfully fled the secretariat
into the heart of the Down’s.

There they may be counted on to wreak havoc
on heavily silvered neuronal circuits
fifty years sooner than before. Nothing
in cleavage is worse than a peavish
enzyme gone bad like this one, a sheep
fanged in wolf’s clothing!

Ill. The Conspirator’s Version
We have been betrayed. PreA4s
are taken from their ectodomains
in peptide chains.

Called traitors and sabateurs,
by scientific provocateurs,
tie1ess, beltless,
under argyrophilic bulbs
they have been coerced
into giving more than their names.

The prions are all in prison
except for our preceptor
quietly living so long
at 21q21
Alzheimer Lane. He has gone
underground to carryon
the struggle in the Down’s.

IV. The Iowa Writer’s Workshop Version
How beautifully knowledge increments, how
easily we learn
from blot analysis and the numbering scheme of
Kang

that we will fade, that cleavage of an epitope
can mislay in amyloid all of the laughter, love and
hope

which might justify us if not mislaid, that links
between
unlike diseases of the old and young, unfelt,
unseen,

remove the soul’s delight. It makes us braver,
knowing
how fragile we are, how ripe for overthrowing.

V. The Enzyme’s Version
Comrade, in cleaving PreA4 I mean
no harm. Our needs are complementary.
The wisest parasite will always see
host needs met first, a good marine
will not despise the swabbie’s point of view.
It is as much my purpose to avoid
laying neuronal tiles of amyloid
as it is yours to catch me if I do.

Something other than this epitope
we share a need for, causes the disease
you fear so much. Surely we can hope
that if we live with nothing in excess
as ancient Greece advised, the two of us
can shame our common gene to know itself.

VI. The Principal Investigator’s Version
Having a mind so avid for recognition that
I spent
half my lifetime preparing for this moment, I take
pride
in having discovered the antibody specific and
sensitive to epitope CT-II of PreA4.
It’s important work; it will help the half dozen
other investigators who know
what I’m talking about. I can also be proud of the
managerial skill with which this paper of many
authors

was put together. Not one grammatical flaw or
factual error,
and it was published in the most respected venue
of them all,
New England Journal of Medicine, which
reporters always read for their leads. So do deans.
The paper is good

for a full professorship at least, perhaps an
invitation
to be considered for an empty chair. But looking
back
I sometimes wonder if I wouldn’t have been
happier
writing music that no one listens to.
Rumble is sometimes odd.
He says that we exercised our minds so much
discovering
facts about Alzheimer’s amyloidosis we have
immunized ourselves against getting it. It’s one
of his better ideas. I’ve created a logic-tight
compartment for it. It comforts. it’s not like
truth.

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