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f?Sychfat 1992. Vol. 16. pp. 883-890

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NEUROTRANSlUITTER CHANGES IN EARLY- hNDIAT;~~~LZHEIMER-

HE11

KENJI KO$AKA2.3,

ICHIHIYti

YOSUKE

ARAI',

and REiJI

TAKASHI

IIZUKA

MOROJI'

1 Department of Psychiatry, Juntendo University school of Uedicine, Tokyo and lpsychiatric Research Institute of Tokyo, Tokyo 156, Japan (Final

form,

January

113

1992)

Abstract Arai, Heii., Yosuke Ichimiya, Kenji Kosaka, Takashi Moroji and Reiji Iizuka: Neurotransnitter Changes in Early- and Late-onset Alzheirer-type Dementia. Prog. Neuro-Psychophamacol. (L Biol. Psychiat. 1992,16(6):883-89D.

1. Neurotransmitter-related 2. 3. 4. 5.

markers were examined in Alzheiuer-type dementia (ATD) and studied whether or not there is biochemical difference between the early- and late-onset sub-groups. Postmorteu brains were obtained from neuropathologically diagnosed ATD with no clinico-neuropathological findings patients and control subjects indicative of neuropsychiatric diseases. Neurochenical data in the early- and late-onset groups were compared to respectively, and the age-matched younger and older control groups, expressed as a percentage of the mean value in the respective controls. Choline acetyltransferase activity and concentrations of serotonin and in the early-onset AT0 group noradrenaline were more severely depleted than in the late-onset ATD group. These findings indicative of heterogeneity of ATD patients were discussed from the pathogenetic and therapeutic viewpoints.

Cxr~~s~saarly"l~~',~~~~~~~~n~~~~n~~~~ot~~~~~~~~e~~ine, Abbreviations: ferase (ChAn

Alrheiner-type

, 5-hydroxyindole-acetic

choline

dementia (ATD), acid (5-HIAA),

choline serotonin

acetyltransacetyltrans(5-HT).

Introduction Alzheimer-type dementia

in

existence several These

the

in

activities,

3Present

(ATD)

elderly.

postmortem

many

one representative biochemical

brains

of

of biogenic

imrunoreactivities

suggest other

address:

is

Recent ATD

of concentrrations

neuropeptide

findings

but also

dementia

the involvement

neurotransmitter

investigations

depletion amines and

of

of not only systems

disease

and their glutamate the

the

enzyme

letabolites,

of

concentration.

cholinergic

(Gottfries,

causes

revealed

of cholinergic

Department of Neuropsychiatry, Yokohama School of Medicine, Yokohama 236, Japan

883

which

1985). City

system

ATD may be University

H.AraietaL

called

a

multi-neurotransmitter

However,

clinical

trials

systems

of replacement

disorder therapy

(Iizuka

for

and Arai

such deficits

1990).

have not

been very successful. According

to neuropathological

ATD) and senile the

single

disease

early-onset

findings,

category

and late-onset

ATD patients

study,

eical

between these two

findings explain

however,

the relatively

neurotransnitter

deficits

we

disease

(late-onset

In clinical

of ATD.

In the present partly

Alzheimer’s

dementia of Alzheimer-type

ATD)

trials,

are usually

(early-onset

are included therefore,

examined simultaneously.

focused on the differences

ATD sub-groups.

poor effects

of

in

both

This

in neuroche-

heterogeneity

replacement

may

therapies

for

in ATD. Methods

Human Brains Postmortem huaan brains with no clinical used

were

were obtained

history

verified

neuropathologi

any neuropathological

findings according

group

of

5 ATD patients

7.4

+

comprised

ATD patients were h)

(82.2

compared and

the

f

with older

respectively.

indicative

9.2

delay

the

(age at death, +

5.8

of

56.0

the brains did not have

illnesses.

f

f

4.6

years,

coaprised

of 5

ATD groups

years,

years,

did not significantly

The sub-

SD 11.6

respectively). + 9.1

subjects

early-onset

sub-group

h,

(> 65 y, n=6, 77.7

The postmortea

ATD and control

and

the younger (< 65 y. n=5, 59.8 controls

All

brains

of neuropsychiatric

to age at onset,

4.8 h) and the late-onset

5.5 years,

and control

disorders.

call y and the control

ATD group was divided postmortem delay,

from ATD cases

of neuropsychiatric

6.4

9.9

differ

f

+

5.9

6.3 h),

between the

groups.

Assessments The activity biogenic previously

of

amines (Arai

choline and their

acetyltransferase metabolites

and

the

concentrations

of

were measured by the methods reported

et al 1984).

Data anal ysi s Mann-Whitney’s

U-test

was used for

statistical

analysis.

Results There

was

no significant

the younger and between netabolites previously

age

older

and

biochemical

in the control (Arai

difference

control brains

et al 1984).

groups, data.

in nor The

brain any

biochemical

data

significant

concentrations

were in good agreement with

between

correlations of

aeines

and

those reported

885

Neurotransmitter changes fn Alzheimer-type dementia

Early-onset

Late-onset

ATD

ATD 100

sup. frontal Orbiti4 Inf. temporal Inwlar Angulate Occipital Cingulate Hippocampus Amygdala 5. innominata Accumbans Caldate Putam.rl Palli&m

M.

Pallidurn L. Thalamus

M

Thalamus

L.

Hypothalamus Mamillary

b.

s. nigra L. coerulaus Raphe lea

Fig 1. .* p