Vascular dementia of Binswanger's type associated with cerebral amyloid angiopathy with the deposition of cystatin C and β-protein

THIRD

that

INTERNATIONAL

in AD,

aB-CR-IR

IR of astrocytes, seems that

CONFERENCE

does not correspondend

and moreover

IrB-Crystallin

the reaction

is a very peculiar

in glia cells under determined

ON ALZHEIMER’S

to the extension

is present HSP

which

that APP is associated with primary defense mechanisms of the brain. Therefore we postulate that APP is involved in the immune response of the periphery and the neuroimmune response associated with plasticity and neurodegeneration. (I) MB&g, U., K6nig. G., Prior, R., Mechkr, H., Schreiter-Gasser. U., Masters, CL.

GFAP-

of

in micro@

cells. It

is probably

s91

DISEASE

produced

conditions.

and Beyxuther, K. (1990) synthesis and secretion of Alzheimer amyloid BA4 precursor

protein by stimulated human peripheral blood leucocytes. WBS L&t. 277: 261-266

359 VASCULAR

DEMENTIA OF BINSWANGER’S

AMYLOID ANGIOPATHY K.IMAOKA,

5. KOBAYASHI,

Third Division

important

S. FUIIHARA,

of Internal

We have reported

TYPE ASSOCIATED

WITH THE DEPOSITION Medicine.

that cystatln

in the pathogenesis

Shimane

Medical

of cerebral

amyloid

In Japanese case as well as hereditary

amyloidosis

in Iceland. Shimode et al establlshed

braln hemorrhage

showed low Cys C levels

by enzyme-linked

lmmunosorbent

of Cys C and D-protein

aemenlla

male, who had history disturbance

and memory

fluld was

for Several

mellitus,

He

had memory

for three years. He was admitted and ataxia

low (56 ng/ml).

Cys C in his

Both of their CT scans

lucency and brain atrophy.

and brain stem

and cortical

to the

He showed

CT scan of case 2 also

lacunes At autopsy, their brains showed multiple

basal ganglia, corona radiata

of

years

leptmenmgeal,

small vessels

positively

with Cys C and D by immunoperoxldase

numberof

senile plaqueswere seen inthecerebralcortex

The amyloid was reacted

(ABC) method. Only small Severe deep white

matterdegeneratlon,whichwascompatlblewlthBinswanger'sdisease,were observed in frontal.parietalandocclpltal of the meningocorticalsegmentof

lobe Amyloiddeposltand

obllteratlon

the long perforatmg arterioles may induce

chronic hypoperfuslonofthedeepwhitematterin

ACTIVATION

SYNTHESIS

(with

The the

medium) with

lmmunologlcal of

?? , F. DEHAUT ?? , W. ?? *, F. DARCY *

JABBOLIR

AHYLOIO *,

actlvatlon secondary to a needle ln,~ury 5-10~1 of sterile protein free culture

l,,JeCtlOn

in different

the The

AND ENHANCEKNT OF bBtaA4 INJURY INTO THE RAT BRAIN

AFTER

parts

of

the

rat

brain

was

studled

together

InductIon of bBtaA4 amylold protein deposits. rapid recruitment of hematogenous cells (monocytes)

followed

as

soon

as

24-36

lIferatIon of mlcrogllal of MHC class II antigen

hours,

cells and C3

by

an

actlvatlon

and

pi-o-

as revealed by the averexpressIon receptor. The actlvatlon peaked

at day 8-15 and slowly decreased. Endothellal cells of some micro-vessels and capillaries were also activated. An astrocytic reaction appeared secondarily in the leslonel area. Such and lmmunoloqlcal activation 1s accompanied by the appearance of bdtaA4

amylold

protein

lmmunoreactlvlty,

mostly

in macro-

phage-like cells, endothellal cells and cortical neurons. The question IS arlsed of the role of macrophages and mlcrogllal cells soluble factors (ILI, TNFalpha, IL6...) in the lmmunologlcal actlvatlon and in amylold precursor protein synthesis and processing. The Immune

result

obtalned

hyperactlvlty

are

present

discussed

In comparison

In Alzhelmer's

patients

Laboratolre de Blologle Cellulalre et Unit+ * Services de Neurologle et Neurochlrurgle CHU d'ANGERS 49033 ANGERS CEDEX 01 FRANCL ??

IhSEBH

with

the

braln. ZYti

??

lacunes at

Amyloid was seen In the wall of

meningeal,

I~NOLOGICAL PROTEIN

A. POUPLARD-BARTHELRIX G. ALHAYEK ?? *, .I. EMILE

IS

cases of

male, who had history

after the stroke, and died of sepsis

abnormally

showed severe perlventricular showed multlple

two autopsied

disturbance

hospital because of developed right sided hemiparesis

cerebrospinal

of CAA with

fluid (570 ng/ml)

with CAA with the deposition

and diabetes

of calculation

marked mental deterioration

with

and dlea oi lung abscess. Case 2 A 74-year-010

of hypertension

and difficulty

(CAA) with brain

that the patients

type associated

iS

hemorrhage

In cerebrospinal

(l3). Case I. A 73-year-old

had bradyklnesla

snowed progressive

cerebral

The

Izumo,Japan

substances

angiopathy

assay. Now we report

dementia of Binswanger’s

hypertension,

University;

C (Cys C) immunoreactive

361

C AND O-PROTEIN,

K. SHIMODE and T.TSUNEMATSU.

hemorrhage

vascular

WITH CEREBRAL

OF CYSTATIN

leucoencephalopathy withCAA

360 The Amyloid Precursor Protein (APP) in Neuro-Immune Reactions U. Mhning~, R. Banat?, G. KS@, C. Czech’, J. Gehrmaonz, G. Kreutzberg*, C. Masters) and K. Beyreutherl ‘Center for Mokcukir Biology, Uaiwrsily of Heidelbq (ZMBH), Im Neuenheimer Feld 282 D-S900 Heidelberg. F.R.G. %kpartmcnt of Newomorphology, Max-Plan&-Institute for Psychiatry, M&cd, F.R.G. tiepartment of Pathology, University of Melbourne, Parkvillc, Vidoria 30X$ Australia

The brain has been considered for a long time as an immunologically privileged site because of the lack of a true lymphatic system and the existence of several barriers that isolate it from the periphery. However, it is known that cells of tbe central nerY0u.s system participate in immunemediated reactions of the brain. The molecular and cellular characteristics of immune and neuro-immune responses suggest that many elements of each system are identical. We have recently shown that APP is involved in immune-mediated responses (1). Immunocytochemical and biochemical studies showed that APP expression is correlated with fundamental processes of T cell activation and initial stages of cell targeting. In order to investigate a possible involvement of APP in neuro-immune reactions we have analysed the APP expression in different cells of the nervous system and have compared their APP-specific biosynthetic behavior to that of T-lymphocytes. From these studies we have concluded

362 AlZHEIMER’S DISEASE: A SYSrrMlC AUTOIMMUNE MSCRDER WITH IMMUNE COMPLEX MfwSfT9 IN PERIPHERAL TISSUES? H. Soinlnen. K. SyrjBnen. S. Syrj6nen. 0. Helnonen. R. Miettinen, H. NeHtaanmBki. and P. Riekklnen. Depts of Neurology; Pathology; Dermatology; University of Kuopio, SF-7021 1 Kuopio, Flnland. Except in the Senile Plaques (SP). NA4 de_amyloid peptide) is known to bs depcsiled in the watls of blood vessels in the brain of petients with Alzheimer% dlsesse (AD). The recent discovery of such #A4 deposfts in and around the denal blood vessels raised the possiblliiy that AD might be a systemic auioknmune disease wRh circulating Immune complexes playing a central role in aggravating lhe clinical symptoms of dementia while precipitating in the brain tissue. We were Interested to find out, whetner such deposfts of the ikt-~nwfle complexes (Le., @/A4, IgG, IgM, C-3) exist in the skin biopsies of AD patlertts. aged cOntro18 and multinfarct dementia (MID) patients. Punch skin biopsies were taken from 35 pstlents (mean age 61~10 years) wnh probable AD, from 9 patients tih possible AD, 15 patients wkh MID (aged 61 f7 years), and from 19 ekieriy nondemented volunteer controls (CO) (aged 6227 years). All subjects underwent clinical neurological lnvestlgetlon and assessment of their cognkhre status by Mini-MentalStatus (MMS) examination. acthrlties of daliy llvlng (APA 1960). and ischemlc score. All patients were permanently hospftallzed and most of them were severely demented. Fommlln-fixed biopsies were embedded in paraffin. and subjected for immunohistcchemical staining using an avldin-biotin-peroxidase (ABC) system snd the following willi.~illai. o/ ~u*i~ui~d ;Y~wpr’fi* w8bdtijijl wsau .LJ.U~SLa synmelir: pefxide comprwng residues 342 of the human #/A4 sequence (gm of Prof. K. Beyreuther), (dlllltion 1 10 4.WO), pofyclonal antibodies to human IgA (120). IgG (1:500), IgM (1:loO). and C3 (1:6.500). Poskive immunoreacthmky was found in the basement membrane, subepldermally, and in and around vascular endothelium. e/A4 deposits were equally present In CO-, probable AD-, possible AD-. and MID patlems. IgG and C3 alone were found more frequently in probable AD- (p