Familial progressive leukoencephalopathy of adult onset

Sill

FOURTH INTERNATIONAL CONFERENCE ON ALZHEIMER’S DISEASE origin. NT andNPTmayrepresent degenerative chanqes and be rather specific events for m. The presence of amyloid plaques but absence of tau-related cytoskeletal patholcqy in non-dementedcases suqqests that 61114peptide is necessary but not sufficient to induce neurofibrillary

pathology. Possibly sane unkovn factors present in non-demented

cases enable neurons to resist cytoskeletal deqeneration. Alternatively, could be oversensitive investiqated.

factors further

or overexpressed in AD brain.

someunknown

This point should

be

risk factors: left atrial hyperfrophy and remote myocardial infarction in the first, insulin-dependent type II diabetes mellitus and congestive heart failure in the second. There was no history of hypertension or seizures. The neuroanatomical distribution of the lesions differed from other types of hippocampal sclerosis linked lo intractable temporal lobe epilepsy, anoxic-ischemic injuries and other metabolic lobe

disorders.

injuries

other

In conclusion,

deafferented

neurodegenerative

siologlcal

we hypothesize

mesial

temporal

disorders,

that the wide extent

structures.

including

as recorded

AD, albeit

of limbii in several

by different

pathophy-

mechanisms

456 FAMILIAL PROGRESSIVE LEUKOENCEPHALOPATHY OF ADULT ONSET. D.S. Knopman, J.H. Sung. Departments of Neurology and Pathology, University of Minnesota, Minneapolis, MN 55455 USA. We rep&t three siblings with a” adult onset dementia with a leukoencephalopathy effecting the fronto-temporo-parietal lobes sparing grey matter. The index cese was a woman who presented at age 59 with depression and bizarre behavior: calling neigh-

bors at odd hours,

hoarding food, impulsively cutting her hair off and neglecting personal hygiene. She had cognitive impairment on mental status exam and-was diagnosed with Alzheimer’s disease. She declined progressively and died at age 64. Pathodegeneration and logically, her brain showed extensive concomitant gliosis of the deeper white matter throughout the cerebrum relative sparing the occipital lobe. Axonal loss end

_

myelin loss were comparable. The U-fibers, corticospinal tracts and optic radiations were spared. Neocortex, hippocampus, striatum, 5. nigra and cerebellum were normal. The medial thalamus

showed moderate cell loss. dementing illness that to be similar clinir?lly.

The second sister presented Th?

age 59 of a nnd VR~ snirl

died at

19 years earlier brain findings were

nearly identical, except that the caudate and medial thalamus showed greater atrophy, cell loss and gliosis. A third sister, still living, was 70 when she first developed difficulties with

and multiple cognitive deficits. depression, functional decline A CT scan showed moderate ventricular dilatation. The clinical histories in these siblings demonstrate that the non-Alzheimer dementias should be suspected when the dementia Dresents in "atvpical" waxs. Disconnection of 1.

cortical and subcortical regions by the white matter disease caused affective disturbances and frontal-lobe-likecognitive and personality changes. These cases are similar to "progressive subcortical gliosis," but the white matter degeneration was more prominent than the gliosis. Perhaps our cases represented a more severe form. A novel late-onset leukodystrophy is possible, but axonal loss was quite prominent. The involvement of subcortical grey matter structures, in particular the medial thalamus and striatum. raises the possibility of a link to dementia lacking distinctive histology, such as mesolimbic dementia, in which subcortical grey matter degeneration is prominent.

458 ATROPHY

OF THE NUCLEUS BASALIS MEYNERTI COMPLEX (NBMC) IN END-STAGE OF ALZHEIMER’S DISEASE. J. Dziewiatkowski, J. Wegiel, H.M. Wisniewski, M. Bobinski, M. Tarnawski, B. Reisberg, M.J. de Leon and DC. Miller. New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, and Aging and Dementia Research Center, New York University Medical Center, NY. The extent of neuronal loss in NBMC in Alzheimefs disease (AD) revealed by several groups shows such variations across studies that the role of this part of the memory system in Alzheimer type dementia becomes unclear. Inclusion of cases at different stages of disease and different methods of characterization of neuronal loss are most probably reasons of these inconsistencies. To control these factors we selected AD cases in end-stage of disease, and we did 3dimensional reconstruction of NBMC. In addition to volume, we examined numerical density and total number of neurons. NBMC was reconstructed from serial sections in two end-stage cases of AD (Functional Assessment Stage 7e; 86- and 77-year old), and in two nondemented cases (88- and 79-years of age). The mean volume of the whole NBMC complex was 114mm3 in control cases and 36mm’ in demented cases (69% atrouhv). L I, The atroohv L < of Ch2., Ch3., and Ch4 reeions was similar in AD cases: 7896, 71% and 65%, respectively. The number of neurons per square millimeter was significantly decreased in AD cases. ‘These data for controls and demented cases were respectively: 64/m& and 36/mm* in Ch2 (44% decrease), 49/mmz and 24/mmz in Ch3 (52% decrease), and 58/mm* and 27/mm2 in Ch4 (54% decrease). Total number of neurons showed even lamer differences beteen control and demented cases: 49,600 versus 5,900 in Ch2 region (88% decrease), 33,000 versus 4,500 in Ch3 region (86% decrease), and 159,900 versus 29,ooO in Ch4 region (82% decrease). This study shows severe neuronal loss in the NBMC in the end stage of AD, and a similar range of atrophic changes in all regions of the NBMC. We also conclude that total number of neurons is a better measure of pathological changes than numerical density. This study was supported in part by funds from the NYS Gffice of Mental Retardation and Developmental Disabilities, and grants from the National Institute of Aging No FGl-AGO-4220, AGO3051 and AGO8051

457 HIPPOCAMPAL INSUFFICIENCY

SCLEROSIS AS A CAUSE

459

SECONDARY TO VASCULAR OF AUHEIMER-LIKE DEMENTIA

ALZHEIHER’S Y. RobifaiNe, A. Leroche-Choloth,

M.Granon, C. Bdtard, and D. Gauvreau

IN

Montreal Oc. CANADA. 1170 brains

year period, gliosis

2 specimens

which

Ammon’s

accessed

was mostly

horn

parasubiculum

and

Neurofibrillary however (AD)

involved slams

with a panel

Mannheim).

Negative

block.

evolution

language onset

at which

Bielschowsky, antibodies

and pathological confusion,

deficits

which

alkaline and

control

of left hemiparesis time. the Hachinsky a gradual

with

Congo

memory

cognitive

methods

Mab

skills,

and

late

loss of autonomy.

deterioration

Both cases shared

for each

worsening

sign

5 year onset

There

shorlly

of was

before

case was that of

lo complete numerous

with

loss of vascular

has

ted

suffered and

of

patient

from

progressive

hypokinesia

atrophy neurilir

spheroids

was

for

of cerebral In and

the

histological degenerative gliosis

study,

by

for

with

ncurofibriIlnry

yellow-brown

pigment of

19

of

years,

widespread there granules

Hallervorden-Spatz

is OR~I

who

rigidity

revealed

tnnglrs nigra

and case

exnainotion Chinese

Autopsy

years.

substantia

B

degeneration

postmortem

B 92-bear-old

cortex

hallmark

either nigral

our

the

Alzheiaer’s

pigaentary

dementia 13

plagues,

amyloidosis. hislopathologic

proved

the

spheroid

Most

that

depletion, In

c.

in

authors. of

nonspecific

deposits. with

nigra

substantia

If. Chinese

demonstrated

llour0oal

disease

many

patients

underwent or

pigment

by

have most

parkinsonism

free

DEGENERATION

Dept.Neurology,

reported

the

disease,

ALzheimer’s repor

been

in

including

changes,

Lab,

studies nigra

Parkinson's

PIGHENTARY K.W.Auang,Q.P.Gui,

Chins. Beijin 100853. findings of extrapyraaidal

clinicopathologir substantia disease

SPHEROID

Neuropathology

PLA General Hospital, A high prevalence Alzheiser’s disease

in

(Boehringer-

WITH

NIGRA.L.N.Wang,

l.I.Jia.

excessive

Red. KlOver-Barrera

score was 7. The second

afier at least 2 years evolution.

the

108s of plaques

were provided

Babinski

in

Alrheimer’s

Histochemical

sections

a lefl

senile for

a l3-amyloid

led lo a complete

off wiihin

and

had a progressively

decreased

reactive

with severe

thresholds

criteria.

a 10

the subiculum

tapered

neurites

diagnostic

Kachaturian’s

of anti-PI-IF

a 77 y.o. 6 who displayed autonomy

gradually

in association

dystrophic

during

hyperlrophic and

which

In the 1st case, an 85 y. $

of mental

sub-acute death,

to

sector

cortex

quantitative

according

program

by a coarse

on Sommer’s

areas,

tangles.

below

the use of modified

paraffin severe

targeted

subicular

remained

a brain bank donor

were characterized

into the transentorhinal

neurons.

disease

through

DISEASE

SUBSTANTIA

Tuang,

CHCN Research Centre. and Dept of Pathology. University of Montreal.

Amongst

THE

diffuse

distribution and were

vascular llll.or0lls which disease.

was